Stiff extracellular matrix activates the transcription factor ATF5 to promote the proliferation of cancer cells.
Seiichiro Ishihara, Atsushi Enomoto, Akihiro Sakai, Tadashi Iida, Shoichiro Tange, Noriyuki Kioka, Akihiro Nukuda, Ayaka Ichikawa Nagasato, Motoaki Yasuda, Takashi Tokino, Hisashi Haga
iScience, 28, 3, 112057, 112057, 21 Mar. 2025, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Cancer tissues are stiffer than normal tissues. Carcinogenesis stiffens the extracellular matrix (ECM) of cancerous tissues, to which cancer cells respond by activating transcription factors, such as YAP/TAZ, Twist1, and β-catenin, which further elevate their malignancy. However, these transcription factors are also expressed in normal tissues. Therefore, inhibiting these factors in order to treat cancer may lead to severe side effects. Here, we show that activating transcription factor 5 (ATF5), highly expressed in tumors, is activated by ECM stiffness and promotes the proliferation of cancer cells, including that of pancreatic cancer cells and lung cancer cells. In addition, ATF5 suppressed the expression of early growth response 1 (EGR1), thereby accelerating cancer cell proliferation. Stiff ECMs trigger the JAK-MYC pathway which activates ATF5. JAK activation was actomyosin independent whereas MYC induction was actomyosin dependent. These results demonstrate the critical role played by ATF5 in the mechanotransduction process seen in cancers.

Matrix stiffness regulates the triad communication of adipocytes/macrophages/endothelial cells through CXCL13.
Arthur Choisez, Seiichiro Ishihara, Takuro Ishii, Yidan Xu, Sepideh D Firouzjah, Hisashi Haga, Ryoichi Nagatomi, Joji Kusuyama
Journal of lipid research, 100620, 100620, 14 Aug. 2024, [Peer-reviewed], [International Magazine]
English, Scientific journal, Adipose tissue remodeling and plasticity are dynamically regulated by the coordinated functions of adipocytes, macrophages, and endothelial cells and extracellular matrix (ECM) that provides stiffness networks in adipose tissue component cells. Inflammation and fibrosis are crucial exogenous factors that dysregulate adipose tissue functions and drastically change the mechanical properties of the ECM. Therefore, communication among the ECM and adipose tissue component cells is necessary to understand the multifaceted functions of adipose tissues. To obtain in vivo stiffness, we utilized genipin as a crosslinker for collagen gels. Meanwhile, we isolated primary adipocytes, macrophages, and endothelial cells from C57BL/6J mice and incubated these cells in the differentiation media on temperature-responsive culture dishes. After the differentiation, these cell sheets were transferred onto genipin-crosslinked collagen gels with varying matrix stiffness. We found that inflammatory gene expressions were induced by hard matrix, whereas anti-inflammatory gene expressions were promoted by soft matrix in all three types of cells. Interestingly, the co-culture experiments of adipocytes, macrophages, and endothelial cells showed that the effects of soft or hard matrix stiffness stimulation on adipocytes were transmitted to the distant adipose tissue component cells, altering their gene expression profiles under normal matrix conditions. Finally, we identified that a hard matrix induces the secretion of CXCL13 from adipocytes, and CXCL13 is one of the important transmitters for stiffness communication with macrophages and endothelial cells. These findings provide insight into the mechano-transmission into distant cells and the application of stiffness control for chronic inflammation in adipose tissues with metabolic dysregulation.

The EGF/EGFR axis and its downstream signaling pathways regulate the motility and proliferation of cultured oral keratinocytes.
Ryota Kobayashi, Emi Hoshikawa, Taisuke Saito, Orakarn Suebsamarn, Eriko Naito, Ayako Suzuki, Seiichiro Ishihara, Hisashi Haga, Kei Tomihara, Kenji Izumi
FEBS open bio, 13, 8, 1469, 1484, 27 May 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, We previously reported that the cell and colony motion of oral keratinocytes are correlated with proliferative capacity, and speculated that this may be a specific index for monitoring cell quality. However, how cell motility and proliferation are regulated by signaling pathways remains unelucidated. Here, we found that the regulation of cell motility and proliferative capacity of oral keratinocytes can be attributed to the epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) axis. The EGFR downstream cascade involving the Src/PI3K/Akt/mTOR signaling pathway showed a major effect on cell motility and proliferative capacity in oral keratinocytes. Furthermore, both EGFR and Src attenuated E-cadherin expression. Taken together, these findings provide a potential basis for future quality control of cells for therapeutic use.

Stiffness-Modulation of Collagen Gels by Genipin-Crosslinking for Cell Culture.
Seiichiro Ishihara, Haruna Kurosawa, Hisashi Haga
Gels (Basel, Switzerland), 9, 2, 10 Feb. 2023, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, The stiffness of extracellular matrices (ECMs) is critical for cellular functions. Therefore, modulating the stiffness of ECMs in vitro is necessary to investigate the role of stiffness in cellular phenomena. Collagen gels are widely used for cell culture matrices in vitro. However, modulation of the stiffness in collagen gels for cell culture is challenging owing to the limited knowledge of the method to increase the stiffness while maintaining low cytotoxicity. Here, we established a novel method to modulate collagen gel stiffness from 0.0292 to 12.5 kPa with low cytotoxicity. We prepared collagens with genipin, a low-cytotoxic crosslinker of amines, at different concentrations and successfully modulated the stiffness of the gels. In addition, on 10 mM genipin-mixed collagen gels (approximately 12.5 kPa), H1299 human lung cancer cells showed spreading morphology and nuclear localization of yes-associated protein (YAP), typical phenomena of cells on stiff ECMs. Mouse mesenchymal stromal cells on 10 mM genipin-mixed collagen gels differentiated to vascular smooth muscle cells. On the other hand, the cells on 0 mM genipin-mixed collagen gels (approximately 0.0292 kPa) differentiated to visceral smooth muscle cells. Our new method provides a novel way to prepare stiffness-modulated collagen gels with low cytotoxicity in cell culture.

Substrate stiffness induces nuclear localization of myosin regulatory light chain to suppress apoptosis.
Katsuya Onishi, Seiichiro Ishihara, Masayuki Takahashi, Akihiro Sakai, Atsushi Enomoto, Kentaro Suzuki, Hisashi Haga
FEBS letters, 01 Feb. 2023, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Stiffness of the extracellular matrix regulates various biological responses, but the response mechanisms are poorly understood. Here, we found that the nuclear diphosphorylated myosin regulatory light chain (2P-MRLC) is a critical mechanomediator that suppresses apoptosis in response to substrate stiffness. Stiff substrates promoted the nuclear localization of 2P-MRLC. Zipper-interacting protein kinase [ZIPK; also known as death-associated protein kinase 3 (DAPK3)], a kinase for MRLC, was localized in the nucleus in response to stiff substrates and promoted the nuclear localization of 2P-MRLC. Moreover, actin fiber formation induced by substrate stiffness promoted the nuclear localization of 2P-MRLC via ZIPK. 2P-MRLC in response to substrate stiffness suppressed the expression of MAF bZIP transcription factor B (MafB) and repressed apoptosis. These findings reveal a newly identified role of MRLC in mechanotransduction.

Improvement of the cell viability of hepatocytes cultured in three-dimensional collagen gels using pump-free perfusion driven by water level difference.
Sumire Ishida-Ishihara, Ryota Takada, Kazuya Furusawa, Seiichiro Ishihara, Hisashi Haga
Scientific reports, 12, 1, 20269, 20269, 24 Nov. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Cell-containing collagen gels are one of the materials employed in tissue engineering and drug testing. A collagen gel is a useful three-dimensional (3D) scaffold that improves various cell functions compared to traditional two-dimensional plastic substrates. However, owing to poor nutrient availability, cells are not viable in thick collagen gels. Perfusion is an effective method for supplying nutrients to the gel. In this study, we maintained hepatocytes embedded in a 3D collagen gel using a simple pump-free perfusion cell culture system with ordinary cell culture products. Flow was generated by the difference in water level in the culture medium. Hepatocytes were found to be viable in a collagen gel of thickness 3.26 (± 0.16 S.E.)-mm for 3 days. In addition, hepatocytes had improved proliferation and gene expression related to liver function in a 3D collagen gel compared to a 2D culture dish. These findings indicate that our perfusion method is useful for investigating the cellular functions of 3D hydrogels.

Mammaglobin 1 mediates progression of trastuzumab-resistant breast cancer cells through regulation of cyclins and NF-κB.
Ratih Kusumastuti, Yuji Kumagai, Seiichiro Ishihara, Atsushi Enomoto, Takashi Murakami, Motoaki Yasuda, Hisashi Haga
FEBS open bio, 12, 10, 1797, 1813, 29 Jul. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Overexpression of human epidermal growth factor receptor 2 (HER2) in various cancers is correlated with poor patient survival. Trastuzumab, a recombinant humanized monoclonal antibody against HER2, has been considered to be a first-line therapy for HER2-positive breast cancer patients, but its usefulness is limited by the development of resistance. In this study, we established resistant cells by long-term treatment with trastuzumab. These cells showed higher proliferation, invasion, and migration abilities than the wild-type cells. Mammaglobin 1 (MGB1), cyclin D1, E1, A2, and phosphorylated NF-κB (p-p65) were upregulated in resistant cells. These proteins regulate cell proliferation, migration, and invasion of resistant cells. Depletion of MGB1 decreased cyclin and p-p65 expression. Cyclin D1 and A2, but not E1 expression, were affected by p-p65 downregulation. In summary, our results indicate that MGB1 expression is increased in breast cancer cells that have gained resistance to trastuzumab, and suggest that MGB1 promotes aggressiveness through cyclin and NF-κB regulation.

Vasculature atrophy causes a stiffened microenvironment that augments epidermal stem cell differentiation in aged skin
Ryo Ichijo, Koichiro Maki, Mio Kabata, Teruasa Murata, Arata Nagasaka, Seiichiro Ishihara, Hisashi Haga, Tetsuya Honda, Taiji Adachi, Takuya Yamamoto, Fumiko Toyoshima
Nature Aging, 2, 7, 592, 600, Springer Science and Business Media LLC, 11 Jul. 2022, [Peer-reviewed]
Scientific journal

The interferon-β/STAT1 axis drives the collective invasion of skin squamous cell carcinoma with sealed intercellular spaces
Yuji Kumagai, Junko Nio-Kobayashi, Seiichiro Ishihara, Atsushi Enomoto, Masashi Akiyama, Ryosuke Ichihara, Hisashi Haga
Oncogenesis, 11, 1, 27, 27, Springer Science and Business Media LLC, 24 May 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Abstract

The process by which cancer cells invade as a cell cluster, known as collective invasion, is associated with metastasis and worse prognosis of cancer patients; therefore, inhibition of collective invasion is considered to improve cancer treatment. However, the cellular characteristics responsible for collective invasion remain largely unknown. Here, we successfully established subclones with various invasive potentials derived from human skin squamous carcinoma cells. The cell cluster of the highly invasive subclone had a hermetically sealed and narrow intercellular space. Interferon-β was localized to the sealed intercellular spaces, leading to collective invasion via the activation of signal transducer and activator of transcription 1 (STAT1). On the other hand, interferon-β was not localized to non-sealed and wide intercellular spaces of the cell cluster of low-invasive subclone with deficient STAT1 activity. In the mixed cell cluster of high- and low-invasive subclones, the high-invasive sub-clonal cells were located at the invasive front of the invasive protrusion, leading to collective invasion by the low-invasive sub-clonal cells. Tissue microarray analysis of human skin squamous cell carcinoma (SCC) also showed enrichment of STAT1 in the invasive front of SCCs. These findings indicate that the intercellular structure controls the potential for collective invasion via STAT1 regulation in SCC.

Pharmacologic conversion of cancer-associated fibroblasts from a protumor phenotype to an antitumor phenotype improves the sensitivity of pancreatic cancer to chemotherapeutics
Tadashi Iida, Yasuyuki Mizutani, Nobutoshi Esaki, Suzanne M. Ponik, Brian M. Burkel, Liang Weng, Keiko Kuwata, Atsushi Masamune, Seiichiro Ishihara, Hisashi Haga, Kunio Kataoka, Shinji Mii, Yukihiro Shiraki, Takuya Ishikawa, Eizaburo Ohno, Hiroki Kawashima, Yoshiki Hirooka, Mitsuhiro Fujishiro, Masahide Takahashi, Atsushi Enomoto
Oncogene, Springer Science and Business Media LLC, 13 Apr. 2022, [Peer-reviewed]
Scientific journal

Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors.
Seiichiro Ishihara, Hisashi Haga
Cancers, 14, 4, 18 Feb. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, Matrix stiffness is critical for the progression of various types of cancers. In solid cancers such as mammary and pancreatic cancers, tumors often contain abnormally stiff tissues, mainly caused by stiff extracellular matrices due to accumulation, contraction, and crosslinking. Stiff extracellular matrices trigger mechanotransduction, the conversion of mechanical cues such as stiffness of the matrix to biochemical signaling in the cells, and as a result determine the cellular phenotypes of cancer and stromal cells in tumors. Transcription factors are key molecules for these processes, as they respond to matrix stiffness and are crucial for cellular behaviors. The Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) is one of the most studied transcription factors that is regulated by matrix stiffness. The YAP/TAZ are activated by a stiff matrix and promotes malignant phenotypes in cancer and stromal cells, including cancer-associated fibroblasts. In addition, other transcription factors such as β-catenin and nuclear factor kappa B (NF-κB) also play key roles in mechanotransduction in cancer tissues. In this review, the mechanisms of stiffening cancer tissues are introduced, and the transcription factors regulated by matrix stiffness in cancer and stromal cells and their roles in cancer progression are shown.

Soft surfaces promote astrocytic differentiation of mouse embryonic neural stem cells via dephosphorylation of MRLC in the absence of serum.
Hiroshi Oyama, Akihiro Nukuda, Seiichiro Ishihara, Hisashi Haga
Scientific reports, 11, 1, 19574, 19574, 01 Oct. 2021, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Astrocytes, which can be obtained from neural stem cells (NSCs) by adding serum and/or recombinant proteins in culture media or by passaging NSCs repeatedly, are expected to be applicable in regenerative medicine for the treatment of neurodegenerative diseases. However, astrocytes obtained using existing methods are costly and have poor quality. The stiffness of culture surfaces has been reported to affect astrocytic differentiation of adult NSCs. However, the influence of surface stiffness on astrocytic differentiation of embryonic NSCs has not yet been reported. In this study, we showed that astrocytic differentiation of embryonic NSCs was increased on soft surfaces (1 kPa and 12 kPa) compared with the NSCs on stiff surfaces (2.8 GPa) in serum-free condition. Furthermore, di-phosphorylated myosin regulatory light chain (PP-MRLC) was decreased in embryonic NSCs cultured on the soft surfaces than the cells on the stiff surfaces. Additionally, astrocytic differentiation of embryonic NSCs was induced by a Ras homolog associated kinase (ROCK) inhibitor, which decreased PP-MRLC in NSCs. These results suggest that decreasing the PP-MRLC of embryonic NSCs on soft surfaces or treating NSCs with a ROCK inhibitor is a good method to prepare astrocytes for application in regenerative medicine.

Osmotic gradient induces stable dome morphogenesis on extracellular matrix.
Sumire Ishida-Ishihara, Masakazu Akiyama, Kazuya Furusawa, Isao Naguro, Hiroki Ryuno, Takamichi Sushida, Seiichiro Ishihara, Hisashi Haga
Journal of cell science, 133, 14, 23 Jun. 2020, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, One of the fundamental processes of morphogenesis is dome formation, but many parts of the mechanisms has been unexplored. Previous in vitro studies showed that osmotic gradient is the driving factor of the dome formation. However, these investigations were performed without extracellular matrix (ECM), which provides structural support to morphogenesis. With the use of ECM, we observed that basal hypertonic stress induced stable domes in vitro that have not been seen in previous studies. These domes developed from the ECM swelling via aquaporin water transport activity. Based on computer simulation, uneven swelling, with a positive feedback between extending cell and enhanced water transport, was a cause for dome formation. These results indicate that osmotic gradient induces dome morphogenesis via both enhanced water transport activity and subsequent ECM swelling.

Biophysical research in Hokkaido University, Japan.
Tomoyasu Aizawa, Makoto Demura, Kazutoshi Gohara, Hisashi Haga, Koichiro Ishimori, Masataka Kinjo, Tamiki Komatsuzaki, Katsumi Maenaka, Min Yao
Biophysical reviews, 12, 2, 233, 236, Apr. 2020, [Peer-reviewed], [International Magazine]
English

Meflin-Positive Cancer-Associated Fibroblasts Inhibit Pancreatic Carcinogenesis.
Mizutani Y, Kobayashi H, Iida T, Asai N, Masamune A, Hara A, Esaki N, Ushida K, Mii S, Shiraki Y, Ando K, Weng L, Ishihara S, Ponik SM, Conklin MW, Haga H, Nagasaka A, Miyata T, Matsuyama M, Kobayashi T, Fujii T, Yamada S, Yamaguchi J, Wang T, Woods SL, Worthley D, Shimamura T, Fujishiro M, Hirooka Y, Enomoto A, Takahashi M
Cancer research, 79, 20, 5367, 5381, Oct. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Cancer-associated fibroblasts (CAF) constitute a major component of the tumor microenvironment. Recent observations in genetically engineered mouse models and clinical studies have suggested that there may exist at least two functionally different populations of CAFs, that is, cancer-promoting CAFs (pCAF) and cancer-restraining CAFs (rCAF). Although various pCAF markers have been identified, the identity of rCAFs remains unknown because of the lack of rCAF-specific marker(s). In this study, we found that Meflin, a glycosylphosphatidylinositol-anchored protein that is a marker of mesenchymal stromal/stem cells and maintains their undifferentiated state, is expressed by pancreatic stellate cells that are a source of CAFs in pancreatic ductal adenocarcinoma (PDAC). In situ hybridization analysis of 71 human PDAC tissues revealed that the infiltration of Meflin-positive CAFs correlated with favorable patient outcome. Consistent herewith, Meflin deficiency led to significant tumor progression with poorly differentiated histology in a PDAC mouse model. Similarly, genetic ablation of Meflin-positive CAFs resulted in poor differentiation of tumors in a syngeneic transplantation model. Conversely, delivery of a Meflin-expressing lentivirus into the tumor stroma or overexpression of Meflin in CAFs suppressed the growth of xenograft tumors. Lineage tracing revealed that Meflin-positive cells gave rise to α-smooth muscle actin-positive CAFs that are positive or negative for Meflin, suggesting a mechanism for generating CAF heterogeneity. Meflin deficiency or low expression resulted in straightened stromal collagen fibers, which represent a signature for aggressive tumors, in mouse or human PDAC tissues, respectively. Together, the data suggest that Meflin is a marker of rCAFs that suppress PDAC progression. SIGNIFICANCE: Meflin marks and functionally contributes to a subset of cancer-associated fibroblasts that exert antitumoral effects.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/20/5367/F1.large.jpg.

Modulation and Characterization of the Double Network Hydrogel Surface-Bulk Transition
Frauenlob Martin, King Daniel R, Guo Honglei, Ishihara Seiichiro, Tsuda Masumi, Kurokawa Takayuki, Haga Hisashi, Tanaka Shinya, Gong Jian Ping
MACROMOLECULES, 52, 17, 6704, 6713, 10 Sep. 2019, [Peer-reviewed]

The intercellular expression of type-XVII collagen, laminin-332, and integrin-β1 promote contact following during the collective invasion of a cancer cell population.
Kumagai Y, Nio-Kobayashi J, Ishida-Ishihara S, Tachibana H, Omori R, Enomoto A, Ishihara S, Haga H
Biochemical and biophysical research communications, 514, 4, 1115, 1121, Jul. 2019, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Cancer cells can invade as a population in various cancer tissues. This phenomenon is called collective invasion, which is associated with the metastatic potential and prognosis of cancer patients. The collectiveness of cancer cells is necessary for collective invasion. However, the mechanism underlying the generation of collectiveness by cancer cells is not well known. In this study, the phenomenon of contact following, where neighboring cells move in the same direction via intercellular adhesion, was investigated. An experimental system was created to observe the two-dimensional invasion using a collagen gel overlay to study contact following in collective invasion. The role of integrin-β1, one of the major extracellular matrix (ECM) receptors, in contact following was examined through the experimental system. Integrin-β1 was localized to the intercellular site in squamous carcinoma cells. Moreover, the intercellular adhesion and contact following were suppressed by treatment of an integrin-β1 inhibitory antibody. ECM proteins such as laminin-332 and type-XVII collagen were also localized to the intercellular site and critical for contact following. Collectively, it was demonstrated that the activity of integrin-β1 and expression of ECM proteins in the intercellular site promote contact following in the collective invasion of a cancer cell population.

Differential contributions of nonmuscle myosin IIA and IIB to cytokinesis in human immortalized fibroblasts.
Yamamoto K, Otomo K, Nemoto T, Ishihara S, Haga H, Nagasaki A, Murakami Y, Takahashi M
Experimental cell research, 376, 1, 67, 76, Mar. 2019, [Peer-reviewed]
English, Scientific journal

Mesenchymal actomyosin contractility is required for androgen-driven urethral masculinization in mice.
Acebedo AR, Suzuki K, Hino S, Alcantara MC, Sato Y, Haga H, Matsumoto KI, Nakao M, Shimamura K, Takeo T, Nakagata N, Miyagawa S, Nishinakamura R, Adelstein RS, Yamada G
Communications biology, 2, 95, 95, 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, The morphogenesis of mammalian embryonic external genitalia (eExG) shows dynamic differences between males and females. In genotypic males, eExG are masculinized in response to androgen signaling. Disruption of this process can give rise to multiple male reproductive organ defects. Currently, mechanisms of androgen-driven sexually dimorphic organogenesis are still unclear. We show here that mesenchymal-derived actomyosin contractility, by MYH10, is essential for the masculinization of mouse eExG. MYH10 is expressed prominently in the bilateral mesenchyme of male eExG. Androgen induces MYH10 protein expression and actomyosin contractility in the bilateral mesenchyme. Inhibition of actomyosin contractility through blebbistatin treatment and mesenchymal genetic deletion induced defective urethral masculinization with reduced mesenchymal condensation. We also suggest that actomyosin contractility regulates androgen-dependent mesenchymal directional cell migration to form the condensation in the bilateral mesenchyme leading to changes in urethral plate shape to accomplish urethral masculinization. Thus, mesenchymal-derived actomyosin contractility is indispensable for androgen-driven urethral masculinization.

Girdin/GIV regulates collective cancer cell migration by controlling cell adhesion and cytoskeletal organization.
Wang X, Enomoto A, Weng L, Mizutani Y, Abudureyimu S, Esaki N, Tsuyuki Y, Chen C, Mii S, Asai N, Haga H, Ishida S, Yokota K, Akiyama M, Takahashi M
Cancer science, 109, 11, 3643, 3656, Nov. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Pathological observations show that cancer cells frequently invade the surrounding stroma in collective groups rather than through single cell migration. Here, we studied the role of the actin-binding protein Girdin, a specific regulator of collective migration of neuroblasts in the brain, in collective cancer cell migration. We found that Girdin was essential for the collective migration of the skin cancer cell line A431 on collagen gels as well as their fibroblast-led collective invasion in an organotypic culture model. We provide evidence that Girdin binds to β-catenin that plays important roles in the Wnt signaling pathway and in E-cadherin-mediated cell-cell adhesion. Girdin-depleted cells displayed scattering and impaired E-cadherin-specific cell-cell adhesion. Importantly, Girdin depletion led to impaired cytoskeletal association of the β-catenin complex, which was accompanied by changes in the supracellular actin cytoskeletal organization of cancer cell cohorts on collagen gels. Although the underlying mechanism is unclear, this observation is consistent with the established role of the actin cytoskeletal system and cell-cell adhesion in the collective behavior of cells. Finally, we showed the correlation of the expression of Girdin with that of the components of the E-cadherin complex and the differentiation of human skin cancer. Collectively, our results suggest that Girdin is an important modulator of the collective behavior of cancer cells.

Anisotropic Multi-channel Collagen Gel (MCCG) Guides the Growth Direction of the Neurite-like Processes of PC12 Cells.
Koh I, Furusawa K, Haga H
Scientific reports, 8, 1, 13901, Sep. 2018, [Peer-reviewed]

Long-term culture of human iPS cell-derived telencephalic neuron aggregates on collagen gel
Hiroshi Oyama, Koji Takahashi, Yoshikazu Tanaka, Hiroshi Takemoto, Hisashi Haga
Cell Structure and Function, 43, 1, 85, 94, Japan Society for Cell Biology, 2018, [Peer-reviewed]
English, Scientific journal

Glycosphingolipid GM2 Induces Invasiveness in Irradiation-tolerant Lung Cancer Cells.
Ishihara S, Aoki K, Mizutani T, Amano M, Nishimura SI, Haga H
Cell structure and function, 43, 2, 177, 185, 2018, [Peer-reviewed]

Mathematical model of collective cell migrations based on cell polarity
Masakazu Akiyama, Takamichi Sushida, Sumire Ishida, Hisashi Haga
Development Growth and Differentiation, 59, 5, 471, 490, Blackwell Publishing, 01 Jun. 2017, [Peer-reviewed]
English, Scientific journal

Utilization of the Student E-Portfolio in the Graduate Education: The Case Report of "Nitobe School Program" in Hokkaido University.
Shotaro Imai, Michiyo Shimamura, Ankit A. Ravankar, Hisashi Haga, Yukinori Kobayashi, Yasuhiro Yamanaka
6th IIAI International Congress on Advanced Applied Informatics(IIAI-AAI), 147, 152, IEEE Computer Society, 2017
International conference proceedings

Mesenchymal stem cells in breast cancer: Response to chemical and mechanical stimuli
Seiichiro Ishihara, Suzanne M. Ponik, Hisashi Haga
Oncoscience, 4, 11-12, 158, 159, Impact Journals LLC, 2017, [Peer-reviewed]
English, Scientific journal

Conformational plasticity of JRAB/MICAL-L2 provides "law and order" in collective cell migration
Ayuko Sakane, Shin Yoshizawa, Masaomi Nishimura, Yuko Tsuchiya, Natsuki Matsushita, Kazuhisa Miyake, Kazuki Horikawa, Issei Imoto, Chiharu Mizuguchi, Hiroyuki Saito, Takato Ueno, Sachi Matsushita, Hisashi Haga, Shinji Deguchi, Kenji Mizuguchi, Hideo Yokota, Takuya Sasaki
MOLECULAR BIOLOGY OF THE CELL, 27, 20, 3095, 3108, Oct. 2016, [Peer-reviewed]
English, Scientific journal

Role of ATF5 in the invasive potential of diverse human cancer cell lines
Akihiro Nukuda, Hiroki Endoh, Motoaki Yasuda, Takeomi Mizutani, Kazushige Kawabata, Hisashi Haga
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 474, 3, 509, 514, Jun. 2016, [Peer-reviewed]
English, Scientific journal

Data set for comparison of cellular dynamics between human AAVS1 locus-modified and wild-type cells
Takeomi Mizutani, Hisashi Haga, Kazushige Kawabata
DATA IN BRIEF, 6, 793, 798, Mar. 2016, [Peer-reviewed]
English, Scientific journal

Heterogeneous filament network formation by myosin light chain isoforms effects on contractile energy output of single cardiomyocytes derived from human induced pluripotent stem cells
Takeomi Mizutani, Kazuya Furusawa, Hisashi Haga, Kazushige Kawabata
REGENERATIVE THERAPY, 3, 90, 96, Mar. 2016, [Peer-reviewed]
English, Scientific journal

Receptor activator of NF-kappa B ligand induces cell adhesion and integrin alpha 2 expression via NF-kappa B in head and neck cancers
Tamaki Yamada, Masumi Tsuda, Takanori Wagatsuma, Yoichiro Fujioka, Mari Fujioka, Aya O. Satoh, Kosui Horiuchi, Shinya Nishide, Asuka Nanbo, Yasunori Totsuka, Hisashi Haga, Shinya Tanaka, Masanobu Shindoh, Yusuke Ohba
SCIENTIFIC REPORTS, 6, 56878, 1, 16, Mar. 2016, [Peer-reviewed]
English, Scientific journal

An improved method for western blotting when extracting proteins from mammalian cells cultured on a collagen gel under serum-free conditions
Seiichiro Ishihara, Takeomi Mizutani, Kazushige Kawabata, Hisashi Haga
CYTOTECHNOLOGY, 68, 1, 25, 32, Jan. 2016, [Peer-reviewed]
English, Scientific journal

Transgene integration into the human AAVS1 locus enhances myosin II-dependent contractile force by reducing expression of myosin binding subunit 85
Takeomi Mizutani, Rui Li, Hisashi Haga, Kazushige Kawabata
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 465, 2, 270, 274, Sep. 2015, [Peer-reviewed]
English, Scientific journal

Stiff substrates increase YAP-signaling-mediated matrix metalloproteinase-7 expression
A. Nukuda, C. Sasaki, S. Ishihara, T. Mizutani, K. Nakamura, T. Ayabe, K. Kawabata, H. Haga
ONCOGENESIS, 4, e165, Sep. 2015, [Peer-reviewed]
English, Scientific journal

Three-dimensional morphogenesis of MDCK cells induced by cellular contractile forces on a viscous substrate
Misako Imai, Kazuya Furusawa, Takeomi Mizutani, Kazushige Kawabata, Hisashi Haga
SCIENTIFIC REPORTS, 5, 14208, 1, 10, Sep. 2015, [Peer-reviewed]
English, Scientific journal

ATF5: development of oncogenic resistance to radiotherapy
Seiichiro Ishihara, Hisashi Haga
AGING-US, 7, 7, 453, 454, Jul. 2015, [Peer-reviewed]
English

基質の硬さによって促進される大腸がん細胞の悪性化 転写因子YAPを介した基質分解酵素MMP-7の発現亢進　　　　　　　　　　　　　　　
温田 晃弘, 石原 誠一郎, 水谷 武臣, 中村 公則, 綾部 時芳, 川端 和重, 芳賀 永
日本細胞生物学会大会講演要旨集, 67回, 168, 168, (一社)日本細胞生物学会, Jun. 2015
Japanese

Compressive Stress Induces Dephosphorylation of the Myosin Regulatory Light Chain via RhoA Phosphorylation by the Adenylyl Cyclase/Protein Kinase A Signaling Pathway
Kenji Takemoto, Seiichiro Ishihara, Takeomi Mizutai, Kazushige Kawabata, Hisashi Haga
PLOS ONE, 10, 3, Mar. 2015, [Peer-reviewed]
English, Scientific journal

Activating transcription factor 5 enhances radioresistance and malignancy in cancer cells
Seiichiro Ishihara, Motoaki Yasuda, Akihiro Ishizu, Masayori Ishikawa, Hiroki Shirato, Hisashi Haga
ONCOTARGET, 6, 7, 4602, 4614, Mar. 2015, [Peer-reviewed]
English, Scientific journal

Secretion of different altered laminin isoforms results in three-dimensional morphological changes in cells cultured on Matrigel
Misako Imai, Takeomi Mizutani, Kazushige Kawabata, Hisashi Haga
2014 International Symposium on Micro-NanoMechatronics and Human Science, MHS 2014, Institute of Electrical and Electronics Engineers Inc., 09 Jan. 2015, [Peer-reviewed]
English, International conference proceedings

Leader cells regulate collective cell migration via Rac activation in the downstream signaling of integrin beta 1 and PI3K
Naoya Yamaguchi, Takeomi Mizutani, Kazushige Kawabata, Hisashi Haga
SCIENTIFIC REPORTS, 5, 7656, Jan. 2015, [Peer-reviewed]
English, Scientific journal

Filamin B enhances the invasiveness of cancer cells into 3D collagen matrices
Yuta Iguchi, Seiichiro Ishihara, Yoshimi Uchida, Kaori Tajima, Takeomi Mizutani, Kazushige Kawabata, Hisashi Haga
Cell Structure and Function, 40, 2, 61, 67, Japan Society for Cell Biology, 2015, [Peer-reviewed]
English, Scientific journal

大腸がん細胞において基質の硬さはミオシンのリン酸化を通じて基質分解酵素MMP7の発現を亢進する(Substrate stiffness enhances expression of matrix metalloproteinase 7 via myosin phosphorylation in colon cancer cells)　　　　　　　　　　　　　　　
温田 晃弘, 石原 誠一郎, 中村 公則, 綾部 時芳, 芳賀 永
日本癌学会総会記事, 73回, P, 3137, (一社)日本癌学会, Sep. 2014
English

Epithelial Sheet Folding Induces Lumen Formation by Madin-Darby Canine Kidney Cells in a Collagen Gel
Sumire Ishida, Ryosuke Tanaka, Naoya Yamaguchi, Genki Ogata, Takeomi Mizutani, Kazushige Kawabata, Hisashi Haga
PLOS ONE, 9, 8, e99655, Aug. 2014, [Peer-reviewed]
English, Scientific journal

Modulation of extracellular conditions prevents the multilayering of the simple epithelium
Takeomi Mizutani, Kazuki Takeda, Hisashi Haga, Mitsugu Todo, Kazushige Kawabata
HISTOCHEMISTRY AND CELL BIOLOGY, 141, 5, 473, 481, May 2014, [Peer-reviewed]
English, Scientific journal

Modulation of extracellular conditions prevents the multilayering of the simple epithelium
Takeomi Mizutani, Kazuki Takeda, Hisashi Haga, Mitsugu Todo, Kazushige Kawabata
HISTOCHEMISTRY AND CELL BIOLOGY, 141, 5, 473, 481, May 2014, [Peer-reviewed]
English, Scientific journal

TRIM27/MRTF-B-Dependent Integrin beta 1 Expression Defines Leading Cells in Cancer Cell Collectives
Takuya Kato, Atsushi Enomoto, Takashi Watanabe, Hisashi Haga, Sumire Ishida, Yuji Kondo, Koichi Furukawa, Takeshi Urano, Shinji Mii, Liang Weng, Maki Ishida-Takagishi, Masato Asai, Naoya Asai, Kozo Kaibuchi, Yoshiki Murakumo, Masahide Takahashi
CELL REPORTS, 7, 4, 1156, 1167, May 2014, [Peer-reviewed]
English, Scientific journal

Coating extracellular matrix proteins on a (3-aminopropyl)triethoxysilane-treated glass substrate for improved cell culture
Hiro-taka Masuda, Seiichiro Ishihara, Ichiro Harada, Takeomi Mizutani, Masayori Ishikawa, Kazushige Kawabata, Hisashi Haga
BIOTECHNIQUES, 56, 4, 172, 179, Apr. 2014, [Peer-reviewed]
English, Scientific journal

2P173 The examination of whether deletion of myosin binding subunit 85 would lead to alteration of cellular mechanical features(12. Cell biology,Poster,The 52nd Annual Meeting of the Biophysical Society of Japan(BSJ2014))
Li Rui, Mizutani Takeomi, Haga Hisashi, Kawabata Kazushige
Seibutsu Butsuri, 54, 1, S223, The Biophysical Society of Japan General Incorporated Association, 2014
English

Substrate stiffness regulates temporary NF-kappa B activation via actomyosin contractions
Seiichiro Ishihara, Motoaki Yasuda, Ichiro Harada, Takeomi Mizutani, Kazushige Kawabata, Hisashi Haga
EXPERIMENTAL CELL RESEARCH, 319, 19, 2916, 2927, Nov. 2013, [Peer-reviewed]
English, Scientific journal

Lung Cancer Cells That Survive Ionizing Radiation Show Increased Integrin alpha 2 beta 1-and EGFR-Dependent Invasiveness
Xue Li, Seiichiro Ishihara, Motoaki Yasuda, Takeshi Nishioka, Takeomi Mizutani, Masayori Ishikawa, Kazushige Kawabata, Hiroki Shirato, Hisashi Haga
PLOS ONE, 8, 8, e70905, Aug. 2013, [Peer-reviewed]
English, Scientific journal

Irradiation-tolerant lung cancer cells acquire invasive ability dependent on dephosphorylation of the myosin regulatory light chain
Seiichiro Ishihara, Motoaki Yasuda, Takeshi Nishioka, Takeomi Mizutani, Kazushige Kawabata, Hiroki Shirato, Hisashi Haga
FEBS LETTERS, 587, 6, 732, 736, Mar. 2013, [Peer-reviewed]
English, Scientific journal

Interruption of glycosphingolipid synthesis enhances osteoarthritis development in mice
Naoki Seito, Tadashi Yamashita, Yukinori Tsukuda, Yuichiro Matsui, Atsushi Urita, Tomohiro Onodera, Takeomi Mizutani, Hisashi Haga, Naoki Fujitani, Yasuro Shinohara, Akio Minami, Norimasa Iwasaki
ARTHRITIS AND RHEUMATISM, 64, 8, 2579, 2588, Aug. 2012, [Peer-reviewed]
English, Scientific journal

1PT230 Evaluation of microtubule deformation by live cell imaging and image analysis(The 50th Annual Meeting of the Biophysical Society of Japan)
Tanaka Ryosuke, Mizutani Takeomi, Haga Hisashi, Kawabata Kazushige
Seibutsu Butsuri, 52, S107, The Biophysical Society of Japan General Incorporated Association, 2012
English

Active fluctuation in the cortical cytoskeleton observed by high-speed live-cell scanning probe microscopy
Kazushi Tamura, Takeomi Mizutani, Hisashi Haga, Kazushige Kawabata
ACTA BIOMATERIALIA, 7, 10, 3766, 3772, Oct. 2011, [Peer-reviewed]
English, Scientific journal

Radiation-induced Cancer Cell Repopulation: A Possible Mechanism Implied by Experiments Using Transplantable Mouse-derived Sarcoma Cell Line
Takeshi Nishioka, Motoaki Yasuda, Tsuguhide Takeshima, Hisashi Haga, Yusuke Miyai, Ken-ichiro Shibata, Rie Yamazaki, Hiroki Shirato, Masahiro Teduka, Hiroyuki Date
CELL STRUCTURE AND FUNCTION, 36, 1, 13, 20, 2011, [Peer-reviewed]
English, Scientific journal

Nano-mechanical properties of living cells expressing constitutively active RhoA effectors
Kazushi Tamura, Takeomi Mizutani, Hisashi Haga, Kazushige Kawabata
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 403, 3-4, 363, 367, Dec. 2010, [Peer-reviewed]
English, Scientific journal

Precise Synthesis and Physicochemical Properties of High-Density Polymer Brushes designed with Poly(N-isopropylacrylamide)
Hiromasa Suzuki, Huda Muhammad Nurul, Takahiro Seki, Taisuke Kawamoto, Hisashi Haga, Kazushige Kawabata, Yukikazu Takeoka
MACROMOLECULES, 43, 23, 9945, 9956, Dec. 2010
English, Scientific journal

Intermediate structure between chromatin fibers and chromosome revealed by mechanical stretching and SPM measurement
Kensuke Ikeda, Takeomi Mizutani, Osamu Hoshi, Tatsuo Ushiki, Hisashi Haga, Kazushige Kawabata
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 400, 1, 181, 186, Sep. 2010
English, Scientific journal

Intermediate structure between chromatin fibers and chromosome revealed by mechanical stretching and SPM measurement
Kensuke Ikeda, Takeomi Mizutani, Osamu Hoshi, Tatsuo Ushiki, Hisashi Haga, Kazushige Kawabata
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 400, 1, 181, 186, Sep. 2010, [Peer-reviewed]
English, Scientific journal

Integrin beta 1-dependent invasive migration of irradiation-tolerant human lung adenocarcinoma cells in 3D collagen matrix
Seiichiro Ishihara, Hisashi Haga, Motoaki Yasuda, Takeomi Mizutani, Kazushige Kawabata, Hiroki Shirato, Takeshi Nishioka
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 396, 3, 651, 655, Jun. 2010, [Peer-reviewed]
English, Scientific journal

1P130 Force Oscillation observed on Pulling Chromosome to Stringlike Fiber(Nucleic acid:Structure & Property,The 48th Annual Meeting of the Biophysical Society of Japan)
HORII TAKUYA, IKEDA KENSUKE, MIZUTANI TAKEOMI, HAGA HISASHI, KAWABATA KAZUSHIGE
Seibutsu Butsuri, 50, 2, S42, The Biophysical Society of Japan General Incorporated Association, 2010
English

2P218 Dynamic Behavior of Cytoskeletons Quantified by Digital Correlation Method(The 48th Annual Meeting of the Biophysical Society of Japan)
Mizutani Takeomi, Ishida Sumire, Hasemi Takatoshi, Hirakawa Yuuki, Kataoka Saya, Tanaka Ryosuke, Nishida Kazuki, Yahara Masao, Takeda Kazuki, Yoshimura Ryo, Kato Munetada, Doi Kenichi, Haga Hisashi, Kawabata Kazushige
Seibutsu Butsuri, 50, 2, S121, The Biophysical Society of Japan General Incorporated Association, 2010
English

Dynamics of leading lamellae of living fibroblasts visualized by high-speed scanning probe microscopy
Kazushi Tamura, Takeomi Mizutani, Hisashi Haga, Kazushige Kawabata
HISTOCHEMISTRY AND CELL BIOLOGY, 133, 1, 59, 67, Jan. 2010, [Peer-reviewed]
English, Scientific journal

Integrin beta1-dependent invasive migration of irradiation-tolerant human lung adenocarcinoma cells in 3D collagen matrix.
Seiichiro Ishihara, Hisashi Haga, Motoaki Yasuda, Takeomi Mizutani, Kazushige Kawabata, Hiroki Shirato, Takeshi Nishioka
Biochemical and biophysical research communications, 396, 3, 651, 655, 2010, [International Magazine]
English, Scientific journal, Radiotherapy is one of the effective therapies used for treating various malignant tumors. However, the emergence of tolerant cells after irradiation remains problematic due to their high metastatic ability, sometimes indicative of poor prognosis. In this study, we showed that subcloned human lung adenocarcinoma cells (A549P-3) that are irradiation-tolerant indicate high invasive activity in vitro, and exhibit an integrin beta1 activity-dependent migratory pattern. In collagen gel overlay assay, majority of the A549P-3 cells displayed round morphology and low migration activity, whereas a considerable number of A549P-3IR cells surviving irradiation displayed a spindle morphology and high migration rate. Blocking integrin beta1 activity reduced the migration rate of A549P-3IR cells and altered the cell morphology allowing them to assume a round shape. These results suggest that the A549P-3 cells surviving irradiation acquire a highly invasive integrin beta1-dependent phenotype, and integrin beta1 might be a potentially effective therapeutic target in combination with radiotherapy.

Mechanical response of single myoblasts to various stretching patterns visualized by scanning probe microscopy
Waka Mitsui, Kazushi Tamura, Takeomi Mizutani, Hisashi Haga, Kazushige Kawabata
ARCHIVES OF HISTOLOGY AND CYTOLOGY, 72, 4-5, 227, 234, Dec. 2009, [Peer-reviewed]
English, Scientific journal

Wide range scanning probe microscopy for probing mechanical effects on cellular function
Takeomi Mizutani, Hisashi Haga, Kosaku Kato, Kazushige Kawabata
ARCHIVES OF HISTOLOGY AND CYTOLOGY, 72, 4-5, 235, 243, Dec. 2009, [Peer-reviewed]
English

Regulation of Cellular Contractile Force in Response to Mechanical Stretch by Diphosphorylation of Myosin Regulatory Light Chain via RhoA Signaling Cascade
Takeomi Mizutani, Kazushige Kawabata, Yoshikazu Koyama, Masayuki Takahashi, Hisashi Haga
CELL MOTILITY AND THE CYTOSKELETON, 66, 7, 389, 397, Jul. 2009, [Peer-reviewed]
English, Scientific journal

Intracellular Particles Involved in Stress Fiber Formation through Remodeling of Actin Filament Networks
Kazushi Tamura, Takeomi Mizutani, Hisashi Haga, Kazushige Kawabata
BIOPHYSICAL JOURNAL, 96, 3, 123A, 123A, Feb. 2009, [Peer-reviewed]
English

Increased Motility and Invasiveness in Tumor Cells That Survive 10 Gy Irradiation
Kaori Tsutsumi, Masumi Tsuda, Natsuka Yazawa, Hirotaka Nakamura, Seiichiro Ishihara, Hisashi Haga, Motoaki Yasuda, Rie Yamazaki, Hiroki Shirato, Hideaki Kawaguchi, Takeshi Nishioka, Yusuke Ohba
CELL STRUCTURE AND FUNCTION, 34, 2, 89, 96, 2009, [Peer-reviewed]
English, Scientific journal

3P-160 Effect on cellular stiffness response to external stretch by memorizing more than 2 cycles of stretch in a myoblast(Cell bioiogy,The 47th Annual Meeting of the Biophysical Society of Japan)
Takemoto Kenji, Mitsui Waka, Tamura Kazushi, Mizutani Takeomi, Haga Hisashi, Kawabata Kazushige
Seibutsu Butsuri, 49, S178, The Biophysical Society of Japan General Incorporated Association, 2009
English

3P-155 Cellular responses to cyclic stretch depending on velocity of the stretch(Cell bioiogy,The 47th Annual Meeting of the Biophysical Society of Japan)
Mizutani Takeomi, Onodera Shin, Haga Hisashi, Kawabata Kazushige
Seibutsu Butsuri, 49, S177, The Biophysical Society of Japan General Incorporated Association, 2009
English

3P-159 Heterogeneous deformation of cytoskeletal network under external stretch processed by digital image correlation method(Cell bioiogy,The 47th Annual Meeting of the Biophysical Society of Japan)
Doi Kenichi, Mizutani Takeomi, Morita Yasuyuki, Uchino Masakazu, Todo Mitsugu, Haga Hisashi, Kawabata Kazushige
Seibutsu Butsuri, 49, S178, The Biophysical Society of Japan General Incorporated Association, 2009
English

3P-158 Dynamics of Microgranular Mechanical Architecture Regulated by Actin Cytoskeleton in Leading Lamella : A Study Using High-Speed Live-Cell SPM(Cell bioiogy,The 47th Annual Meeting of the Biophysical Society of Japan)
Tamura Kazushi, Mizutani Takeomi, Haga Hisashi, Kawabata Kazushige
Seibutsu Butsuri, 49, S177, S178, The Biophysical Society of Japan General Incorporated Association, 2009
English

Displacement of actin filament and actin binding proteins under local deformation processed by digital image correlation method in a myoblast
Takeomi Mizutani, Kenichi Doi, Yasuyuki Morita, Masakazu Uchino, Mitsugu Todo, Hisashi Haga, Kazushige Kawabata
Journal of Biomechanical Science and Engineering, 4, 3, 415, 422, 2009, [Peer-reviewed]
English, Scientific journal

Novel Function of Transcription Factor ATF5: Blockade of p53-dependent Apoptosis Induced by Ionizing Irradiation
Takeshi Nishioka, Yusuke Miyai, Hisashi Haga, Kazushige Kawabata, Hiroki Shirato, Akihiro Homma, Kenichiro Shibata, Motoaki Yasuda
CELL STRUCTURE AND FUNCTION, 34, 1, 17, 22, 2009, [Peer-reviewed]
English, Scientific journal

Mechanical response to isotropic shrinkage of fibroblasts measured by scanning probe microscopy
Taisuke Kawamoto, Hisashi Haga, Kazushi Tamura, Takeomi Mizutani, Kazushige Kawabata
JAPANESE JOURNAL OF APPLIED PHYSICS, 47, 7, 6173, 6176, Jul. 2008
English, Scientific journal

1S8-2 Collective movement and morphogenesis of epithelial cells(1S8 Intra- and inter-cellular mechanical communications on collective movements of cells,The 46th Annual Meeting of the Biophysical Society of Japan)
Haga Hisashi
Seibutsu Butsuri, 48, S6, S7, The Biophysical Society of Japan General Incorporated Association, 2008
English

3P-167 F-actin aggregates appearing during stress fiber formation : their possible role in reorganization of F-actin networks into stress fibers(The 46th Annual Meeting of the Biophysical Society of Japan)
Tamura Kazushi, Mizutani Takeomi, Haga Hisashi, Kawabata Kazushige
Seibutsu Butsuri, 48, S153, The Biophysical Society of Japan General Incorporated Association, 2008
English

2P-250 Visualization of three-dimensional synaptic morphology of living hippocampal neurons by Scanning Probe Microscope(The 46th Annual Meeting of the Biophysical Society of Japan)
JIANG Jun, MIZUTANI Takeomi, HAGA Hisashi, KUDOH Suguru, TAGUCHI Takahisa, KAWABATA Kazushige
Seibutsu Butsuri, 48, S113, The Biophysical Society of Japan General Incorporated Association, 2008
English

Matrixmetalloproteinases: Up-regulated in subclones that survived 10-Gy irradiation
Takeshi Nishioka, Motoaki Yasuda, Kaori Tsutsumi, Hisashi Haga, Hiroki Shirato
Radiation Medicine - Medical Imaging and Radiation Oncology, 25, 8, 430, 431, Oct. 2007, [Peer-reviewed]
English

Visualization of stretch-induced intracellular tensional response of single fibroblasts by mechanical scanning probe microscopy
Kazushi Tamura, Takeomi Mizutani, Hisashi Haga, Kazushige Kawabata
JAPANESE JOURNAL OF APPLIED PHYSICS PART 1-REGULAR PAPERS BRIEF COMMUNICATIONS & REVIEW PAPERS, 46, 8B, 5631, 5635, Aug. 2007
English, Scientific journal

Development of a device to stretch tissue-like materials and to measure their mechanical properties by scanning probe microscopy
Takeomi Mizutani, Hisashi Haga, Kazushige Kawabata
ACTA BIOMATERIALIA, 3, 4, 485, 493, Jul. 2007, [Peer-reviewed]
English, Scientific journal

Imaging mechanical properties of living cells by scanning probe microscopy
Hisashi Haga, Masafumi Nagayama, Kazushige Kawabata
CURRENT NANOSCIENCE, 3, 1, 97, 103, Feb. 2007
English, Scientific journal

3P192 Cell morphology and cell-matrix adhesion inducing collective movement of epithelial cells on a collagen gel substrate(Cell biological problems-adhesion, motility, cytoskeleton, signaling, and membrane,Poster Presentations)
Ogura Hayato, Hayashi Kanako, Mizutani Takeomi, Kawabata Kazushige, Haga Hisashi
Seibutsu Butsuri, 47, S251, The Biophysical Society of Japan General Incorporated Association, 2007
English

3P199 Intracellular particles moving along actin stress fibers visualized by time-lapse scanning probe microscopy(Cell biological problems-adhesion, motility, cytoskeleton, signaling, and membrane,Poster Presentations)
Tamura Kazushi, Mizutani Takeomi, Haga Hisashi, Kawabata Kazushige
Seibutsu Butsuri, 47, S252, The Biophysical Society of Japan General Incorporated Association, 2007
English

1P130 Novel intermediate structure between chromatin fiber and chromosome revealed by mechanical stretch and SPM measurement(Protein engineering, evolutionary engineering, nucleic acid-binding proteins, and nucleic acid,Oral Presentations)
Ikeda Kensuke, Hoshi Osamu, Ushiki Tatsuo, Mizutani Takeomi, Haga Hisashi, Kawabata Kazushige
Seibutsu Butsuri, 47, S56, The Biophysical Society of Japan General Incorporated Association, 2007
English

Novel beads-and-chain structure of unraveling human chromosomes by mechanical stretching
Kensuke Ikeda, Osamu Hoshi, Tatsuo Ushiki, Hisashi Haga, Kazushige Kawabata
BIOPHYSICAL JOURNAL, 52A, 52A, Jan. 2007, [Peer-reviewed]
English

Three-dimensional tumor cell movement in collagen gel: mesenchymal-to-amoeboid transition in a sub-clone that survived 10 Gy irradiation
T. Nishioka, H. Haga, Y. Miyai, M. Yasuda, K. Tsutsumi, R. Yamazaki, H. Shirato, K. Kawabata
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 69, 3, S148, S148, 2007
English

Collective Movement and Morphogenesis of Epithelial Cells　　　　　　　　　　　　　　　
Proceedings of the international symposium on topological aspects of critical systems and networks, 82, 85, 2007

Diphosphorylation of the myosin regulatory light chain enhances the tension acting on stress fibers in fibroblasts
Takeomi Mizutani, Hisashi Haga, Yoshikazu Koyama, Masayuki Takahashi, Kazushige Kawabata
JOURNAL OF CELLULAR PHYSIOLOGY, 209, 3, 726, 731, Dec. 2006, [Peer-reviewed]
English

The role of actin-binding protein filamin A in cellular stiffness and morphology studied by wide-range scanning probe microscopy
K Kato, Y Ohmori, T Mizutani, H Haga, K Ohashi, T Ito, K Kawabata
JAPANESE JOURNAL OF APPLIED PHYSICS PART 1-REGULAR PAPERS BRIEF COMMUNICATIONS & REVIEW PAPERS, 45, 3B, 2328, 2332, Mar. 2006
English, Scientific journal

Observation of stiff domain structure on collagen gels by wide-range scanning probe microscopy
T Mizutani, H Haga, K Kato, K Matsuda, K Kawabata
JAPANESE JOURNAL OF APPLIED PHYSICS PART 1-REGULAR PAPERS BRIEF COMMUNICATIONS & REVIEW PAPERS, 45, 3B, 2353, 2356, Mar. 2006
English, Scientific journal

2P529 Tensional Responses of Single Living Cells to External Stretch Visualized by SPM(52. Bio-imaging,Poster Session,Abstract,Meeting Program of EABS & BSJ 2006)
Tamura Kazushi, Mizutani Takeomi, Haga Hisashi, Kawabata Kazushige
Seibutsu Butsuri, 46, 2, S428, The Biophysical Society of Japan General Incorporated Association, 2006
English

2P176 New filamentous ordered structure appeared by stretching of unfixed human chromosome(36. DNA to chromatin,Poster Session,Abstract,Meeting Program of EABS & BSJ 2006)
Ikeda Kensuke, Hoshi Osamu, Ushiki Tatsuo, Haga Hisashi, Kawabata Kazushige
Seibutsu Butsuri, 46, 2, S339, The Biophysical Society of Japan General Incorporated Association, 2006
English

Static friction of agar gels: Formation of contact junctions at frictional interface
T Nitta, H Kato, H Haga, K Nemoto, K Kawabata
JOURNAL OF THE PHYSICAL SOCIETY OF JAPAN, 74, 11, 2875, 2879, Nov. 2005
English, Scientific journal

Visualization of elasticity distribution of single human chromosomes by scanning probe microscopy
K Nomura, O Hoshi, D Fukushi, T Ushiki, H Haga, K Kawabata
JAPANESE JOURNAL OF APPLIED PHYSICS PART 1-REGULAR PAPERS BRIEF COMMUNICATIONS & REVIEW PAPERS, 44, 7B, 5421, 5424, Jul. 2005
English, Scientific journal

Spatiotemporal variation in cellular stiffness corresponding to development of morphological polarity
S Toko, T Mizutani, H Haga, K Kawabata
JAPANESE JOURNAL OF APPLIED PHYSICS PART 1-REGULAR PAPERS BRIEF COMMUNICATIONS & REVIEW PAPERS, 44, 7B, 5451, 5454, Jul. 2005
English, Scientific journal

Collective movement of epithelial cells on a collagen gel substrate
H Haga, C Irahara, R Kobayashi, T Nakagaki, K Kawabata
BIOPHYSICAL JOURNAL, 88, 3, 2250, 2256, Mar. 2005, [Peer-reviewed]
English, Scientific journal

2SD05 Tensional Homeostasis: Stabilization of Intracellular Tension Responding to External Stress
Mizutani T., Haga H., Takahashi M., Koyama Y., Kawabata K.
Seibutsu Butsuri, 45, S22, The Biophysical Society of Japan General Incorporated Association, 2005
Japanese

3SF52 Instrumentation of Nano-Force Scanning Probe Microscopy and the Application to Cell Biology
Haga H.
Seibutsu Butsuri, 45, S30, The Biophysical Society of Japan General Incorporated Association, 2005
Japanese

2P129 Step-like elongation of a single chromosome on mechanical stretching
Ikeda K., Hoshi O., Ushiki T., Haga H., Kawabata K.
Seibutsu Butsuri, 45, S152, The Biophysical Society of Japan General Incorporated Association, 2005
Japanese

1P338 Mechanical responses of single living cell to elongation and contraction : Development of a measuring system using SPM
Tamura K., Mizutani T., Haga H., Kawabata K.
Seibutsu Butsuri, 45, S116, The Biophysical Society of Japan General Incorporated Association, 2005
Japanese

Cellular stiffness response to external deformation: Tensional homeostasis in a single fibroblast
T Mizutani, H Haga, K Kawabata
CELL MOTILITY AND THE CYTOSKELETON, 59, 4, 242, 248, Dec. 2004, [Peer-reviewed]
English, Scientific journal

Contribution of cellular contractility to spatial and temporal variations in cellular stiffness
M Nagayama, H Haga, M Takahashi, T Saitoh, K Kawabata
EXPERIMENTAL CELL RESEARCH, 300, 2, 396, 405, Nov. 2004, [Peer-reviewed]
English, Scientific journal

Wide-range scanning probe microscopy for visualizing biomaterials in the submillimeter range
T Mizutani, H Haga, K Nemoto, K Kawabata
JAPANESE JOURNAL OF APPLIED PHYSICS PART 1-REGULAR PAPERS SHORT NOTES & REVIEW PAPERS, 43, 7B, 4525, 4528, Jul. 2004
English, Scientific journal

2P203 Tensional Home-ostasis of a Single Cell Regulated by Phosphorylation of the Myosin Regulatory Light Chain
Mizutani T., Haga H., Takahashi M., Kawabata K.
Seibutsu Butsuri, 44, S160, The Biophysical Society of Japan General Incorporated Association, 2004
Japanese

Micro-viscoelasticity evaluation of living cell
NAGAYAMA Masafumi, HAGA Hisashi, TANAKA Yoshio, HIRAI Yoshihiko, KAWABATA Kazushige
kenbikyo, 38, 2, 90, 93, The Japanese Society of Microscopy, 31 Jul. 2003
Japanese

Visualization of dynamic organization of cytoskeleton gels in living cells by hybrid-SPM
K Kawabata, Y Sado, M Nagayama, T Nitta, K Nemoto, Y Koyama, H Haga
CHINESE JOURNAL OF POLYMER SCIENCE, 21, 2, 169, 174, Mar. 2003
English, Scientific journal

Cellular migration coordinated by cortical tension
Nagayama M., Haga H., Takahashi M., Kawabata K.
Seibutsu Butsuri, 43, S108, The Biophysical Society of Japan General Incorporated Association, 2003
Japanese

Cooperative movement of epithelial cells induced by orientation of collagen gel fibers
Irahara C., Haga H., Kawabata K.
Seibutsu Butsuri, 43, S109, The Biophysical Society of Japan General Incorporated Association, 2003
Japanese

Recovery of Tension from Streching or Shortening Stress in Fibroblasts
Mizutani T., Haga H., Kawabata K.
Seibutsu Butsuri, 43, S162, The Biophysical Society of Japan General Incorporated Association, 2003
Japanese

Microdomain structure of agar gels observed by mechanical-scanning probe microscopy
T Nitta, Y Endo, H Haga, K Kawabata
JOURNAL OF ELECTRON MICROSCOPY, 52, 3, 277, 281, 2003, [Peer-reviewed]
English, Scientific journal

Time dependent static friction force of agar gel-on-glass plate immersed in water
T Nitta, H Haga, K Kawabata
JOURNAL DE PHYSIQUE IV, 12, PR9, 319, 320, Nov. 2002
English, Scientific journal

Improvement of force modulation mode with scanning probe microscopy for imaging viscoelasticity of living cells
M Nagayama, H Haga, Y Tanaka, Y Hirai, M Kabuto, K Kawabata
JAPANESE JOURNAL OF APPLIED PHYSICS PART 1-REGULAR PAPERS SHORT NOTES & REVIEW PAPERS, 41, 7B, 4952, 4955, Jul. 2002
English, Scientific journal

3N0915 Cooperative Movement and Polarity Formation of Epithelial Cells on Soft Collagen Gel
Haga H., Hirakawa N., Irahara T., Hayashi K., Takahashi M., Kawabata K.
Seibutsu Butsuri, 42, 2, S194, The Biophysical Society of Japan General Incorporated Association, 2002
Japanese

3G0900 Mechanical Response of Fibroblast to External Stress Using Elastic Substratums
Mizutani T., Haga H., Kawabata K.
Seibutsu Butsuri, 42, 2, S162, The Biophysical Society of Japan General Incorporated Association, 2002
Japanese

3G0930 Mechanical-SPM measurement for fibroblasts on restricted contact area
Miyashita H., Haga H., Kawabata K.
Seibutsu Butsuri, 42, 2, S163, The Biophysical Society of Japan General Incorporated Association, 2002
Japanese

Drastic change of local stiffness distribution correlating to cell migration in living fibroblasts
M Nagayama, H Haga, K Kawabata
CELL MOTILITY AND THE CYTOSKELETON, 50, 4, 173, 179, Dec. 2001
English, Scientific journal

Differential localization of non-muscle myosin II isoforms and phosphorylated regulatory light chains in human MRC-5 fibroblasts
T Saitoh, S Takemura, K Ueda, H Hosoya, M Nagayama, H Haga, K Kawabata, A Yamagishi, M Takahashi
FEBS LETTERS, 509, 3, 365, 369, Dec. 2001
English, Scientific journal

Dynamical coordinative mechanism in cell movement
Nagayama M., Haga H., Kawabata K.
Seibutsu Butsuri, 41, S207, The Biophysical Society of Japan General Incorporated Association, 2001
Japanese

Dynamic responses to external stress of living cells using SPM
Sado Y., Haga H., Kawabata K.
Seibutsu Butsuri, 41, S93, The Biophysical Society of Japan General Incorporated Association, 2001
Japanese

Evaluation of Viscoelasticity of Biological Cells in Liquid by Scanning Probe Microscopy
Yoshio Tanaka, Yoshihiko Hirai, Masaaki Kabuto, Kazushige Kawabata, Hisashi Haga, Masahumi Nagayama
Nihon Kikai Gakkai Ronbunshu, C Hen/Transactions of the Japan Society of Mechanical Engineers, Part C, 67, 663, 3498, 3504, 2001, [Peer-reviewed]
English, Scientific journal

Mechanical effects on collective phenomena of biological systems: cell locomotion
Kazushige Kawabata, Masafumi Nagayama, Hisashi Haga, Takashi Sambongi
CURRENT APPLIED PHYSICS, 1, 1, 66, 71, Jan. 2001
English, Scientific journal

Viscoelastic imaging of mechanical structure related to cell locomotion in AFM
HAGA Hisashi, KAWABATA Kazushige
kenbikyo, 35, 3, 276, 278, The Japanese Society of Microscopy, 30 Nov. 2000
Japanese

Mechanical properties of membrane surface of cultured astrocyte revealed by atomic force microscopy
H Shiga, Y Yamane, E Ito, K Abe, K Kawabata, H Haga
JAPANESE JOURNAL OF APPLIED PHYSICS PART 1-REGULAR PAPERS SHORT NOTES & REVIEW PAPERS, 39, 6B, 3711, 3716, Jun. 2000
English, Scientific journal

Elasticity mapping of living fibroblasts by AFM and immunofluorescence observation of the cytoskeleton
H Haga, S Sasaki, K Kawabata, E Ito, T Ushiki, T Sambongi
ULTRAMICROSCOPY, 82, 1-4, 253, 258, Feb. 2000
English, Scientific journal

Comparing microscopic with macroscopic elastic properties of polymer gel
T Nitta, H Haga, K Kawabata, K Abe, T Sambongi
ULTRAMICROSCOPY, 82, 1-4, 223, 226, Feb. 2000
English, Scientific journal

Evolving elasticity distribution of living cells
Nagayama M., Haga H., Kawabata K.
Seibutsu Butsuri, 40, S80, The Biophysical Society of Japan General Incorporated Association, 2000
Japanese

Visualization of cytoskeleton network and elastisity distribution of living cells using hybrid-AFM
Sado Y., Haga H., Matsuoka I., Kawabata K.
Seibutsu Butsuri, 40, S182, The Biophysical Society of Japan General Incorporated Association, 2000
Japanese

Three-dimensional characterization of interior structures of exocytotic apertures of nerve cells using atomic force microscopy
T Tojima, Y Yamane, H Takagi, T Takeshita, T Sugiyama, H Haga, K Kawabata, T Ushiki, K Abe, T Yoshioka, E Ito
NEUROSCIENCE, 101, 2, 471, 481, 2000
English, Scientific journal

Quantitative analyses of topography and elasticity of living and fixed astrocytes
Y Yamane, H Shiga, H Haga, K Kawabata, K Abe, E Ito
JOURNAL OF ELECTRON MICROSCOPY, 49, 3, 463, 471, 2000
English, Scientific journal

Time-lapse viscoelastic imaging of living fibroblasts using force modulation mode in AFM
H Haga, M Nagayama, K Kawabata, E Ito, T Ushiki, T Sambongi
JOURNAL OF ELECTRON MICROSCOPY, 49, 3, 473, 481, 2000
English, Scientific journal

Big softer hole on living cells: Elasticity imaging with AFM
K Kawabata, H Haga, T Nitta, Y Endo, M Nagayama, E Ito, T Sambongi
SCANNING AND FORCE MICROSCOPIES FOR BIOMEDICAL APPLICATIONS II, 3922, 91, 98, 2000
English, International conference proceedings

Dynamics of astrocyte adhesion as analyzed by a combination of atomic force microscopy and immunocytochemistry: the involvement of actin filaments and connexin 43 in the early stage of adhesion
Y Yamane, H Shiga, H Asou, H Haga, K Kawabata, K Abe, E Ito
ARCHIVES OF HISTOLOGY AND CYTOLOGY, 62, 4, 355, 361, Oct. 1999
English, Scientific journal

原子間力顕微鏡による生きた細胞の粘弾性マッピング
川端 和重, 芳賀 永, 三本木 孝
日本バイオレオロジー学会誌(B&R) = Journal of Japanese Society of Biorheology, 13, 3, 29, 37, 特定非営利活動法人 日本バイオレオロジー学会, 30 Sep. 1999
Japanese

Atomic force microscopic observation of three-dimensional morphological changes of neurons where stimulated by a neurotransmitter
T Hosono, M Yamanaka, T Tojima, Y Yamane, H Sadamoto, D Hatakeyama, H Haga, K Kawabata, K Abe, E Ito
JAPANESE JOURNAL OF APPLIED PHYSICS PART 1-REGULAR PAPERS SHORT NOTES & REVIEW PAPERS, 38, 6B, 3940, 3945, Jun. 1999
English, Scientific journal

Viscoelastic Measurements on Cells in Cultured Medium Using Atomic Force Microscopy
KAWABATA Kazushige, HAGA Hisashi
Seibutsu Butsuri, 39, 3, 179, 181, The Biophysical Society of Japan General Incorporated Association, May 1999
Japanese

Surface structures of cultured type 2 astrocytes revealed by atomic force microscopy
Y Yamane, D Hatakeyama, H Haga, K Abe, E Ito
ZOOLOGICAL SCIENCE, 16, 1, 1, 7, Feb. 1999
English, Scientific journal

Atomic force microscopic and immunocytochemical study of glial cell to cell adhesion.
Yamane Y., Shiga H., Asou H., Haga H., Kawabata K., Abe K., Ito E.
Seibutsu Butsuri, 39, S57, The Biophysical Society of Japan General Incorporated Association, 1999
Japanese

Elasticity Mapping of Living Cells by AFM and Immunofluorescence Observation of Cytoskeleton.
Haga H., Sasaki S., Kawabata K., Ito E., Ushiki T., Sambongi T.
Seibutsu Butsuri, 39, S37, The Biophysical Society of Japan General Incorporated Association, 1999
Japanese

Imaging Viscoelasticity of Living Cells using Force Modulation Mode in AFM
Nagayama M., Haga H., Kawabata K., Ito E., Sambongi T.
Seibutsu Butsuri, 39, S37, The Biophysical Society of Japan General Incorporated Association, 1999
Japanese

Elastic Measurement with AFM : its quantitativeness.
NITTA Takahiro, HAGA Hisashi, KAWABATA Kazusige, ABE Kazuhiro, SAMBONGI Takashi
Seibutsu Butsuri, 39, S36, The Biophysical Society of Japan General Incorporated Association, 1999
Japanese

Time dependent viscoelastic image of living nerve cells using AFM
K Kawabata, H Ishizuka, T Nitta, H Haga, E Ito, K Abe, T Ushiki, T Sambongi
BIOLOGICAL PHYSICS, 487, 235, 239, 1999
English, International conference proceedings

Thermal and structural study close to a smecticA-smecticA critical point
P Gorria, P Barois, HT Nguyen, G Sigaud, L Navailles, CW Garland, H Haga
MOLECULAR CRYSTALS AND LIQUID CRYSTALS SCIENCE AND TECHNOLOGY SECTION A-MOLECULAR CRYSTALS AND LIQUID CRYSTALS, 330, 1419, 1426, 1999
English, Scientific journal

Spatial and temporal viscoelastic imaging of living fibroblasts by atomic force microscopy
H Haga, S Sasaki, K Kawabata, E Ito, K Abe, T Sambongi
BIOLOGICAL PHYSICS, 487, 229, 234, 1999
English, International conference proceedings

Imaging elastic properties of soft materials immersed in water using force modulation mode in atomic force microscopy
H Haga, S Sasaki, M Morimoto, K Kawabata, E Ito, K Abe, T Sambongi
JAPANESE JOURNAL OF APPLIED PHYSICS PART 1-REGULAR PAPERS SHORT NOTES & REVIEW PAPERS, 37, 6B, 3860, 3863, Jun. 1998
English, Scientific journal

Elastic properties of living fibroblasts as imaged using force modulation mode in atomic force microscopy
S Sasaki, M Morimoto, H Haga, K Kawabata, E Ito, T Ushiki, K Abe, T Sambongi
ARCHIVES OF HISTOLOGY AND CYTOLOGY, 61, 1, 57, 63, Mar. 1998
English, Scientific journal

Calorimetric study of the smectic-A-hexatic-B transition in 3(10)OBC
H Haga, CW Garland
PHYSICAL REVIEW E, 57, 1, 603, 609, Jan. 1998, [Peer-reviewed]
English, Scientific journal

Calorimetric study of the smectic-A－hexatic-B transition in 3(10)OBC
HAGA H, GARLAND C W
PHYSICAL REVIEW E, 57, 1, 603, 609, 1998

Influence of nematic range on birefringence, heat capacity and elastic modulus near a nematic-smectic-A phase transition
F Beaubois, T Claverie, JP Marcerou, JC Rouillon, HT Nguyen, CW Garland, H Haga
PHYSICAL REVIEW E, 56, 5, 5566, 5574, Nov. 1997
English, Scientific journal

Thermal study of the influence of aerosils on the phase transitions of heptyloxybenzylidene butylaniline
H Haga, CW Garland
LIQUID CRYSTALS, 23, 5, 645, 652, Nov. 1997
English, Scientific journal

Effect of silica aerosil particles on liquid-crystal phase transitions
H Haga, CW Garland
PHYSICAL REVIEW E, 56, 3, 3044, 3052, Sep. 1997
English, Scientific journal

Calorimetric study of heptyloxybenzylidene butylaniline in silica aerogels
H Haga, CW Garland
LIQUID CRYSTALS, 22, 3, 275, 277, Mar. 1997
English, Scientific journal

Quasicritical heat capacity at a smectic-A-hexatic-B phase transition
HAGA H, KUTNJAK Z, IANNACCHIONE G S, QIAN S, FINOTELLO D, GARLAND C W
PHYSICAL REVIEW E, 56, 2, 1808, 1818, 1997

Evaluation of the specific heat anomaly of RS(1-x)-ARS(x)
N Noda, H Nakano, H Haga, R Nozaki, Y Shiozaki
JOURNAL OF THE KOREAN PHYSICAL SOCIETY, 29, S513, S516, Nov. 1996, [Peer-reviewed]
English, Scientific journal

Thermal properties of improper ferroelectric Tb2(MoO4)3: Critical phenomena and traces of isomorphic phase transition
B. A. Strukov, A. Onodera, S. A. Taraskin, I. V. Shnaidshtein, B. S. Red'kin, H. Haga
Ferroelectrics, 185, 1-4, 181, 184, Taylor and Francis Inc., 1996, [Peer-reviewed]
English, Scientific journal

A CALORIMETRIC STUDY OF THE (ROCHELLE SALT)(1-x) - (AMMONIUM ROCHELLE SALT)(x) MIXED CRYSTAL SYSTEM
Natsuko Noda, Hisashi Haga, Hidehiko Nakano, Ryusuke Nozaki, Yoichi Shiozaki
FERROELECTRICS, 184, 293, 296, 1996, [Peer-reviewed]
English, Scientific journal

PREASYMPTOTIC 3D XY CRITICAL-BEHAVIOR OF HEAT-CAPACITY AT NORMAL-INCOMMENSURATE PHASE-TRANSITION IN K2ZNCL4 AND K2SEO4
H HAGA, R NOZAKI, Y SHIOZAKI, K EMA
JOURNAL OF THE PHYSICAL SOCIETY OF JAPAN, 64, 11, 4258, 4264, Nov. 1995, [Peer-reviewed]
English, Scientific journal

Three Dimensional XY Critical Behavior of Heat Capacity at Normal-Incommensurate Phase Transition in Rb2ZnCl4
Hisashi Haga, Akira Onodera, Yoichi Shiozaki, Kenji Ema, Hideaki Sakata
Journal of the Physical Society of Japan, 64, 3, 822, 829, 1995, [Peer-reviewed]
English, Scientific journal

A calorimetric study of RS1-xARSx mixed crystal system (0.9 ≤ x ≤ 1.0)
Natsuko Noda, Hisashi Haga, Toshio Kikuta, Ryusuke Nozaki, Yoichi Shiozaki
Ferroelectrics, 168, 1, 169, 175, 1995, [Peer-reviewed]
English, Scientific journal

Thermal and dielectric studies on ferroelectric (CH3NHCH2COOH)3CaCl2 (TSCC)
Hisashi Haga, Akira Onodera, Haruyasu Yamashita, Yoichi Shiozaki
Ferroelectrics, 159, 1, 55, 60, 01 Sep. 1994, [Peer-reviewed]
English, Scientific journal

SPECIFIC HEAT AND CRITICAL BEHAVIOR IN THIOUREA AT NORMAL-INC PHASE TRANSITION
Akira Onodera, Hisashi Haga, Francoise Denoyer, Jean Godart, Yoichi Shiozaki
FERROELECTRICS, 155, 305, 310, 1994, [Peer-reviewed]
English, Scientific journal

KINETIC EVOLUTION IN THE INCOMMENSURATE PHASE IN K2ZnCl4
Akira Onodera, Oto Watanabe, Haruyasu Yamashita, Hisashi Haga, Yoichi Shiozaki
FERROELECTRICS, 155, 299, 304, 1994, [Peer-reviewed]
English, Scientific journal

DIELECTRIC BEHAVIOR AND RELAXATION PROCESS IN MODULATED PHASES IN THIOUREA
Akira Onodera, Oto Watanabe, Haruyasu Yamashita, Hisashi Haga, Yoichi Shiozaki
FERROELECTRICS, 155, 311, 316, 1994, [Peer-reviewed]
English, Scientific journal

Thermal and Dielectric Properties of a New Ferroelectric LaBGeO5
Akira Onodera, Hisashi Haga, Boris A. Strukov, Alexander A. Belov, Sergei A. Taraskin, Haruyasu Yamashita, Yoshiaki Uesu
Journal of the Physical Society of Japan, 62, 12, 4311, 4315, 1993, [Peer-reviewed]
English, Scientific journal

New Phase Transition in Ferroelectric (CH3NHCH2COOH)3CaCl2 at Low Temperatures
Hisashi Haga, Akira Onodera, Yoichi Shiozaki, Haruyasu Yamashita
Journal of the Physical Society of Japan, 62, 6, 1857, 1859, 1993, [Peer-reviewed]
English, Scientific journal

Critical Behaviour of Specific Heat in Ferroelectric K2Z11CI4 and (NH4)2BeF4 at Normal-Incommensurate Phase Transition
Hisashi Haga, Akira Onodera
Journal of the Physical Society of Japan, 62, 5, 1597, 1602, 1993, [Peer-reviewed]
English, Scientific journal

Specific heat and critical indices associated with normal-incommensurate phase transition in K2ZnCl4 and (NH4)2BeF4
Hisashi Haga, Akira Onodera, Yoichi Shiozaki
Ferroelectrics, 125, 1, 123, 128, 01 Jan. 1992, [Peer-reviewed]
English, Scientific journal

Dielectric properties and phase transition in cesium tetrachlorozincate Cs2ZnCl4
Akira Onodera, Oto Watanabe, Hisashi Haga, Toshio Kikuta, Eisuke Suzuki, Haruyasu Yamashita, Yoichi Shiozaki, Haruyasu Yamashita
Ferroelectrics, 125, 1, 141, 146, 01 Jan. 1992, [Peer-reviewed]
English, Scientific journal

ゲル基質上の上皮細胞シートが引き起こす浸透圧勾配依存的なドーム形成とその数理モデル
秋山正和, 石原(石田)すみれ, 須志田隆道, 芳賀永, 日本応用数理学会年会講演予稿集(CD-ROM), 2020, 2020

Osmotic gradient-dependent pattern formation induced by epithelial cell sheet and its mathematical model
秋山正和, 石原(石田)すみれ, 須志田隆道, 芳賀永, 日本数理生物学会年会(Web), 30th, 2020

Fascin1により発現亢進されるLGR5は乳がんの浸潤を促進する(LGR5 up-regulated by Fascin1 promotes breast cancer cell invasion)　　　　　　　　　　　　　　　
伊東 祐紀, 石原 誠一郎, 加野 将之, 松原 久裕, 芳賀 永, 日本癌学会総会記事, 78回, P, 3249, Sep. 2019
(一社)日本癌学会, English

細胞・組織動態解析と数理モデルで解く形態形成の原理 細胞の集団運動と3次元形態形成に対する数理的アプローチ　　　　　　　　　　　　　　　
秋山 正和, 須志田 隆道, 森 瞳, 石田 すみれ, 芳賀 永, 日本生化学会大会プログラム・講演要旨集, 92回, [2S15a, 07], Sep. 2019
(公社)日本生化学会, Japanese

上皮細胞シートの折り返しによる管腔形成と細胞極性　　　　　　　　　　　　　　　
芳賀 永, 医学のあゆみ, 268, 6, 507, 511, Feb. 2019
Japanese, Introduction scientific journal

Collective Movement and 3D Morphogenesis of Epithelial Cells Induced by Softness of the Extracellular Matrix
HAGA Hisashi, Seibutsu Butsuri, 58, 4, 196, 199, 2018
<p>Collective movement and 3D morphogenesis are essential events in diverse physiological processes. We found that epithelial cells (MDCK cells) move collectively along one direction on a soft collagen gel, whereas the cells migrate randomly on a rigid collagen-coated-glass. Moreover, lumen formation occurred when an epithelial sheet on a collagen gel was overlaid with another collagen gel. We also found that MDCK cells formed 3D morphology on top of the Matrigel. The appearance of the morphologies was like a tulip hat. The cells tugged at the peripheral matrix and remodeled the gel surface. In this mini-review, these dynamical behaviors of the epithelial cells are discussed in terms of the cellular contractile force and viscoelasticity of the extracellular matrix.</p>, The Biophysical Society of Japan General Incorporated Association, Japanese, Introduction scientific journal

RANKLによるインテグリンα2の発現亢進はインテグリンβ2の細胞内輸送を介して細胞接着を亢進する
大場雄介, 山田珠希, 山田珠希, 山田珠希, 津田真寿美, 藤岡容一朗, 藤岡真理, 堀内浩水, 堀口美香, 佐藤絢, ネパール ブラバ, 王せい, 柏木彩花, 西出真也, 南保明日香, 芳賀永, 田中伸哉, 進藤正信, 日本生理学雑誌(Web), 79, 2, 49 (WEB ONLY), 49, May 2017
(一社)日本生理学会, Japanese

Fascin-1による転写因子Stat3を介したがん細胞の浸潤促進　　　　　　　　　　　　　　　
高橋 都史樹, 温田 晃弘, 加野 将之, 松原 久裕, 芳賀 永, 日本癌学会総会記事, 75回, P, 1094, Oct. 2016
(一社)日本癌学会, English

Activating transcription factor 5 promotes cancer cell invasion through transcriptional activation of integrins
A. Nukuda, H. Endoh, S. Ishihara, M. Yasuda, T. Mizutani, K. Kawabata, H. Haga, MOLECULAR BIOLOGY OF THE CELL, 26, 2015
English, Summary international conference

Lung cancer cells after irradiation indicate viability and malignancy dependent on activating transcription factor 5.
S. Ishihara, M. Yasuda, A. Ishizu, H. Haga, MOLECULAR BIOLOGY OF THE CELL, 25, Dec. 2014
English, Summary international conference

Rac1-, PI3K-, and integrin-beta 1-dependent leader cells that are essential for the collective migration of MDCK cells
N. Yamaguchi, T. Mizutani, K. Kawabata, H. Haga, MOLECULAR BIOLOGY OF THE CELL, 24, 2013
English, Summary international conference

放射線により誘発されるがん細胞の再増殖 : 移植可能なマウス肉腫細胞を用いた実験から類推されるメカニズム
西岡 健, 安田 元昭, 武島 嗣英, 芳賀 永, 宮井 優介, 柴田 健一郎, 山崎 理衣, 白土 博樹, 手塚 正博, 伊達 広行, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 87, 4, 192, 192, 01 Aug. 2012
Japanese

Regulatory mechanism of integrin beta 1 expression in collectively migrating cancer cells.
T. Kato, A. Enomoto, H. Haga, S. Ishida, M. Asai, N. Asai, M. Takahashi, MOLECULAR BIOLOGY OF THE CELL, 23, 2012
English, Summary international conference

EGFR and Integrin alpha 2 beta 1 Dependent Invasiveness of Lung Adenocarcinoma Cells that Survived 10 Gy Ionizing Radiation.
X. Li, S. Ishihara, M. Yasuda, T. Mizutani, K. Kawabata, T. Nishioka, H. Haga, MOLECULAR BIOLOGY OF THE CELL, 23, 2012
English, Summary international conference

Involvement of cell polarity and cell migration in folding phenomena of epithelial sheets
S. Ishida, R. Tanaka, N. Yamaguchi, T. Mizutani, K. Kawabata, H. Haga, MOLECULAR BIOLOGY OF THE CELL, 23, 2012
English, Summary international conference

細胞骨格・細胞運動・細胞移動 ラミニンを含む軟らかいゲル基質上でみられる上皮細胞集団の3次元形態形成(Cytoskeleton/ Cell motility/ Cell migration 3D Morphogenesis of Epithelial Cells on a Soft Substrate Containing Laminin Induced by Cellular Contractile Force)　　　　　　　　　　　　　　　
今井 美沙子, 水谷 武臣, 川端 和重, 芳賀 永, 日本細胞生物学会大会講演要旨集, 63回, 118, 118, May 2011
(一社)日本細胞生物学会, English

3D Morphogenesis of Epithelial Cells on a Laminin-rich Soft Substrate Induced by Cellular Contractile Force
M. Imai, T. Mizutani, K. Kawabata, H. Haga, MOLECULAR BIOLOGY OF THE CELL, 22, 2011
English, Summary international conference

Substrate stiffness regulates NF-kB expression and activity in cancer cells
S. Ishihara, M. Yasuda, T. Mizutani, K. Kawabata, H. Haga, MOLECULAR BIOLOGY OF THE CELL, 22, 2011
English, Summary international conference

Increased Invasiveness and Non-spheroid Morphology Change of Human Lung Adenocarcinoma Cells That Survived 10 Gy Irradiation
T. Nishioka, S. Ishihara, Y. Miyai, T. Mizutani, K. Kawabata, H. Shirato, R. Yamazaki, M. Yasuda, H. Haga, K. Kawabata, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 75, 3, S540, S540, 2009
English, Summary international conference

走査型プローブ顕微鏡による細胞機能の解析
水谷武臣, 芳賀永, 加藤幸作, 川端和重, 細胞, 40, 6, 250, 253, 20 Jun. 2008
ニューサイエンス社, Japanese

Spatial Distribution of Elasticity in Living Cell Surfaces Imaged by Scanning Probe Microscopy
HAGA Hisashi, MIZUTANI Takeomi, KAWABATA Kazushige, Journal of the Surface Science Society of Japan, 29, 4, 235, 238, 10 Apr. 2008
日本表面科学会, Japanese

Novel function of transcription factor ATF5: Blockade of p53-dependent apoptosis induced by irradiation
T. Nishioka, M. Yasuda, H. Haga, R. Yamazaki, K. Tsutsumi, H. Shirato, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 72, 1, S43, S43, 2008
English, Summary international conference

30pXG-5 Thermal effects on static frictions of agar gels
Inazuki Y., Haga H., Nemoto K., Kawabata K., Meeting abstracts of the Physical Society of Japan, 61, 1, 338, 338, 04 Mar. 2006
The Physical Society of Japan (JPS), Japanese

Instrumentation of Wide-Range Scanning Probe Microscopy and the Applications to Cell Biology and Biomaterial Science
MIZUTANI Takeomi, HAGA Hisashi, KAWABATA Kazushige, Biophysics, 45, 2, 105, 108, 25 Mar. 2005
The Biophysical Society of Japan, Japanese

Collective movement of epithelial cells on collagen gel substrate
H Haga, C Irahara, R Kobayashi, T Nakagaki, K Kawabata, BIOPHYSICAL JOURNAL, 88, 1, 429A, 429A, Jan. 2005
English, Summary international conference

細胞のダイナミクスと集団運動(ソフトマターの物理学2004-変形と流動-,研究会報告)
水谷 武臣, 芳賀 永, 川端 和重, 物性研究, 83, 3, 333, 334, 20 Dec. 2004
この論文は国立情報学研究所の電子図書館事業により電子化されました。, 物性研究刊行会, Japanese

Domain like structure of human-chromosome observed by mechanical scanning probe microscopy
K Kawabata, K Nomura, H Haga, O Hoshi, D Fukushi, T Ushiki, MOLECULAR BIOLOGY OF THE CELL, 15, 329A, 329A, Nov. 2004
English, Summary international conference

Tensional homeostasis of a single fibroblast regulated by phosphorylation of the myosin regulatory light chain
M Takeomi, H Haga, M Takahashi, K Kawabata, MOLECULAR BIOLOGY OF THE CELL, 15, 159A, 159A, Nov. 2004
English, Summary international conference

Collective and unidirectional movement of epithelial cells on a collagen gel substrate
H Haga, K Hayashi, K Kawabata, MOLECULAR BIOLOGY OF THE CELL, 15, 179A, 179A, Nov. 2004
English, Summary international conference

14aTC-9 Temperature effect of static friction of agar gels
Kawabata K., Kato H., Nitta T., Nemoto K., Haga H., Meeting abstracts of the Physical Society of Japan, 59, 2, 232, 232, 25 Aug. 2004
The Physical Society of Japan (JPS), Japanese

29pWA-4 Static friction of polymer gels : waiting time dependence of real contact area
Kato H., Nitta T., Haga H., Nemoto K., Kawabata K., Meeting abstracts of the Physical Society of Japan, 59, 1, 309, 309, 03 Mar. 2004
The Physical Society of Japan (JPS), Japanese

高分子ゲルの静止摩擦の待機時間効果 : 真実接触領域の直接観察(摩擦の物理,研究会報告)
加藤 秀章, 新田 高洋, 芳賀 永, 川端 和重, 物性研究, 81, 6, 860, 863, 2004
物性研究刊行会, Japanese

Time-Lapse Observation of Local Stiffness Distribution Correlating to Cell Migration Using Nano-Force SPM
HAGA Hisashi, NAGAYAMA Masafumi, TAKAHASHI Masayuki, KAWABATA Kazushige, バイオエンジニアリング講演会講演論文集, 2003, 15, 19, 20, 20 Jan. 2003
The Japan Society of Mechanical Engineers, Japanese

Cooperative movement of epithelial cells on soft collagen gel
H Haga, N Hirakawa, T Iarahara, K Hayashi, M Takahashi, Y Kawabata, MOLECULAR BIOLOGY OF THE CELL, 13, 78A, 78A, Nov. 2002
English, Summary international conference

Cellular migration driven by relaxation of cortical tension imaged with mechanical force microscopy
M Nagayama, H Haga, M Takahashi, K Kawabata, MOLECULAR BIOLOGY OF THE CELL, 13, 193A, 193A, Nov. 2002
English, Summary international conference

Sliding friction of polymer gel : Static friction III
Nitta Takahiro, Kawabata Kazushige, Haga Hisashi, Meeting abstracts of the Physical Society of Japan, 57, 2, 211, 211, 13 Aug. 2002
The Physical Society of Japan (JPS), Japanese

Mechanical Observation of Living Cells Using Hybrid-Scanning Probe Microscopy
KAWABATA Kazushige, SADO Yasuhiro, NAGAYAMA Masafumi, HAGA Hisashi, Japanese journal of optics, 31, 6, 483, 488, 10 Jun. 2002
応用物理学会分科会日本光学会, Japanese

24pXK-13 Sliding friction of polymer gel : Static friction II
Nitta Takahiro, Haga Hisashi, Kawabata Kazushige, Meeting abstracts of the Physical Society of Japan, 57, 1, 241, 241, 01 Mar. 2002
The Physical Society of Japan (JPS), Japanese

Stiffness change of living fibroblasts depending on cell motion
M Nagayama, H Haga, K Kawabata, MOLECULAR BIOLOGY OF THE CELL, 12, 171A, 171A, Nov. 2001
English, Summary international conference

919 Evaluation of Viscoelasticity of Biomaterials in Liquid by Atomic Force Microscope
TANAKA Yoshio, Hirai Yoshihiko, Kabuto Masaaki, KAWABATA Kazushige, HAGA Hisashi, NAGAYAMA Masahumi, 関西支部講演会講演論文集, 2001, 76, "9, 43"-"9-44", 16 Mar. 2001
Knowledge of viscoelasticity distribution of a living biological cell is useful for investigation of a relationship between its motility and cellular structure. This paper proposes a strict evaluation method of viscoelasticity of cells through vibration analysis of AFM cantilever in water by considering resistance force of cells against cantilever tip penetration and drag force of water due to the cantilever vibration. Cyclic penetration of the tip is presently given by the vibration of the table, while additional vertical motion is applied to the table to avoid the effect of. topography on the evaluation of the viscoelasticity. A map of viscoelasticity distribution is taken by scanning motion of the table., The Japan Society of Mechanical Engineers, Japanese

Temporal and Spatial Viscoelastic Imaging of Cell Locomotion by AFM
NAGAYAMA M., HAGA H., KAWABATA K., SAMBONGI T., 電子顕微鏡, 35, 359, 359, 01 May 2000
Japanese

Local Elastic Modulus Mapping of Ager Gel with AFM
Nitta T., Haga H., Kawabata K., Abe K., Sambongi T., Meeting abstracts of the Physical Society of Japan, 55, 1, 285, 285, 10 Mar. 2000
The Physical Society of Japan (JPS), Japanese

液中環境における生きた細胞の粘弾性マッピング
川端 和重, 芳賀 永, Molecular electronics and bioelectronics, 10, 4, 215, 220, 29 Oct. 1999
Japanese

Imaging the Viscoelasticity of Living Cell with AFM(III)
Haga H., Sasaki S., Nitta T., Kawabata K., Ito E., Abe K., Sambongi T., Biophysics, 38, 2, S144, 07 Sep. 1998
The Biophysical Society of Japan General Incorporated Association, Japanese

Atomic Force Microscopic Observation of Fine Surface Structures Which Reflect Cytoskeletons in Glial Cells
YAMANE Y., HATAKEYAMA D., HAGA H., KAWABATA K., ABE K., ITO E., Meeting abstracts of the Physical Society of Japan, 53, 2, 857, 857, 05 Sep. 1998
The Physical Society of Japan (JPS), Japanese

Imaging Viscoclasticity of Living Fibroblast with AFM(II)~Fine Morphology of lamellipodia and its time dependence~
SASAKI S., HAGA H., KAWABATA K., ITO E., ABE K., SAMBONGI T., Meeting abstracts of the Physical Society of Japan, 53, 1, 737, 737, 10 Mar. 1998
The Physical Society of Japan (JPS), Japanese

Imaging Viscoelasticity of Living Nerve Cell with AFM(III)~Fine Globular Morphology in the Peripheral Region~
HAGA H., MORIMOTO M., SASAKI S., KAWABATA K., ITO E., ABE K., SAMBONGI T., Meeting abstracts of the Physical Society of Japan, 53, 1, 738, 738, 10 Mar. 1998
The Physical Society of Japan (JPS), Japanese

8a-P-4 Imaging the Viscoelasticity of Living Cell with AFM
Haga H., Morimoro M., Sasaki S., Kawabata K., Ito E., Abe K., Sambongi T., Meeting abstracts of the Physical Society of Japan, 52, 2, 853, 853, 16 Sep. 1997
The Physical Society of Japan (JPS), Japanese

29p-YD-7 The study of the first order phase transition with AC calorimetory IV
Nakano H., Noda N., Haga H., Nozaki R, Shiozaki Y., Meeting abstracts of the Physical Society of Japan, 52, 1, 138, 138, 17 Mar. 1997
The Physical Society of Japan (JPS), Japanese

29p-YD-4 Specific Heat of RS-ARS Mixed Crystals IV
Noda N., Nakano H., Haga H., Nozaki R., Shiozaki Y., Meeting abstracts of the Physical Society of Japan, 52, 1, 137, 137, 17 Mar. 1997
The Physical Society of Japan (JPS), Japanese

3a-R-11 The study of the first order phase transition with AC calorimetry III
Nakano H., Noda N., Haga H., Nozaki R., Shiozaki Y., Abstracts of the meeting of the Physical Society of Japan. Annual meeting, 51, 2, 116, 116, 15 Mar. 1996
The Physical Society of Japan (JPS), Japanese

3a-R-6 Specific Heat of RS-ARS Mixed Crystal System III
Noda N., Nakano H., Haga H., Nozaki R., Shiozaki Y., Abstracts of the meeting of the Physical Society of Japan. Annual meeting, 51, 2, 114, 114, 15 Mar. 1996
The Physical Society of Japan (JPS), Japanese

28a-YD-11 The Complex Specific Heat of RS-ARS
Nakano H., Noda N., Haga H., Nozaki R., Shiozaki Y., Abstracts of the meeting of the Physical Society of Japan. Sectional meeting, 1995, 2, 95, 95, 12 Sep. 1995
The Physical Society of Japan (JPS), Japanese

The Study of The First Order Phase Transition by AC Calorimetry II
Noda N., Nakano H., Haga H., Nozaki R., Shiozaki Y., Abstracts of the meeting of the Physical Society of Japan. Annual meeting, 50, 3, 673, 673, 16 Mar. 1995
The Physical Society of Japan (JPS), Japanese

Specific Heat of (RS)_<1-x>-(ARS)_x Mixed Crystals 0≤x<0.9
Noda N, Nakano H, Haga H, Nozaki R, Shiozaki Y, Abstracts of the meeting of the Physical Society of Japan. Annual meeting, 50, 2, 101, 101, 16 Mar. 1995
The Physical Society of Japan (JPS), Japanese

"D-E hysteresis Measurement of the Mixed Crystals RS_<(1-x)>-ARS_x (0.18
Toki H, Nakano H, Haga H, Nozaki R, Shiozaki Y, Abstracts of the meeting of the Physical Society of Japan. Annual meeting, 50, 2, 101, 101, 16 Mar. 1995
The Physical Society of Japan (JPS), Japanese

2p-B-3 The Study of The First Order Phase Transition By AC Calorimetry
Noda N, Nakano H, Haga H, Nozaki R, Shiozaki Y, Abstracts of the meeting of the Physical Society of Japan. Sectional meeting, 1994, 3, 544, 544, 16 Aug. 1994
The Physical Society of Japan (JPS), Japanese

15p-J-8 Specific heat of(RS)_<1-X>-(ARS)_X mixed crystals 0.9
Noda N., Haga H., Kikuta T., Nozaki R., Shiozaki Y., Abstracts of the meeting of the Physical Society of Japan. Sectional meeting, 1993, 2, 122, 122, 20 Sep. 1993
The Physical Society of Japan (JPS), Japanese

実験医学 増刊 『線維化 : 慢性疾患のキープロセス』 組織の「硬さ」から迫る線維症研究の新展開
石原 誠一郎, 芳賀 永, 第4章 第4節
羊土社, Aug. 2020, 9784758103886, 196p, Japanese, [Joint work]

三次元培養における培養手法と周辺技術動向　　　　　　　　　　　　　　　
芳賀 永, 三次元培養法（ハイドロゲル法）
情報機構, Apr. 2019, [Joint work]

Chromosome Nanoscience and Technology　　　　　　　　　　　　　　　
TAYLOR & FRANCIS GROUP, 2007

生物系の統計力学　　　　　　　　　　　　　　　
北海道大学理学部

生物系の量子力学　　　　　　　　　　　　　　　
北海道大学理学部

少人数討論型育成プログラム　　　　　　　　　　　　　　　
北海道大学大学院生命科学院

Search for novel cancer therapeutic molecular targets from the stemness induction mechanism of adenovirus E4 genes.
Grants-in-Aid for Scientific Research
01 Apr. 2024 - 31 Mar. 2027
安田 元昭, 芳賀 永, 義達 理恵子
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 24K13103

Investigation of cell-cell adhesion structures and signaling pathways causing collective invasion in cancer cells
Grants-in-Aid for Scientific Research
01 Apr. 2021 - 31 Mar. 2024
芳賀 永
多くのがん細胞種は細胞間の接着を維持したまま集団で浸潤する．このことを集団浸潤という．その機序については不明な点が多い．本研究は，がん細胞にみられる細胞間接着構造と細胞間に形成される仮足構造を観察・解析するとともに，それらの構成分子およびシグナル経路を明らかにすることで集団浸潤の普遍的機序に迫る．研究目的で掲げた3つの問いである①集団浸潤をもたらすシグナル経路の探索，②細胞間に特異的に見られる仮足構造の解析，③集団浸潤の普遍性の検証のうち，令和3年度では，①集団浸潤をもたらすシグナル経路の探索を行った．
ヒト皮膚扁平上皮がん細胞株（A431細胞）から高浸潤と低浸潤のサブクローン株を樹立し，DNAマイクロアレイによってサブクローン間の発現遺伝子を比較したところ，これまでにkeratin-1，10，14，JAK-STAT経路などの遺伝子発現に有意な差があることが明らかとなっていた．そこで，転写因子であるSTAT1に着目し，RNA干渉法によってSTAT1の発現を抑制したところ，高浸潤サブクローン株の集団浸潤が有意に抑制されるという結果を得た．さらに，STAT1を活性化させるサイトカインであるインターフェロンβ（INFB）の発現と局在を免疫蛍光染色法によって観察したところ，高浸潤サブクローン株では細胞-細胞間にINFBが局在する一方，低浸潤サブクローン株では細胞-細胞間での局在は観察されなかった．加えて，高浸潤サブクローン株でINFBの発現をノックダウンしたところ，STAT1は活性化せず，集団浸潤も抑制されることが明らかとなった．さらに，EGTAを用いて細胞-細胞間接着を緩めたところ，高浸潤サブクローン株におけるINFBの細胞-細胞間局在が消失し，集団浸潤が抑制された．これらの結果は，IFNBが細胞間隙に蓄積しSTAT1が活性化することで集団浸潤が誘引されることを示している．
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 21K07142

足場材の硬さの違いを利用した上皮角化・非角化様式解明と培養口腔粘膜作成法への応用
科学研究費助成事業 基盤研究(B)
01 Apr. 2020 - 31 Mar. 2023
泉 健次, 芳賀 永, 石原 誠一郎, 加来 賢, 佐藤 大祐, 鈴木 絢子
今年度は、コロナの影響で魚うろこコラーゲンの入手がままならず、既製品の魚うろこコラーゲンであるセルキャンパスしか手に入らなかったため、コラーゲンゲルの足場材の硬さをランダムに変えての培養口腔粘膜作成はできなかった。その分、セルキャンパスを用いて、コントロールの硬い培養皿面、同表面でカルシウム濃度をあげた分化培地、および、いわゆるコラーゲンゲルの軟性面で培養したケラチノサイトに対し、運動能解析と外注によるマイクロアレイ解析による網羅的遺伝子発現分析（現在までに2サンプル解析終了し、現在もう2サンプル培養しており、外注予定）を実施し、結果がでたら新たに分担者に加わっていただいた凌先生にヒートマップとクラスター図を作成してもらい、ビッグデータ解析をお願いする。
細胞運動能解析では驚いたことに、コラーゲンゲル上の細胞運動能が、硬い培養皿面での細胞運動能より上回っていた。これは、いわゆる癌細胞のメカノバイオロジーと真逆の現象である。さらに、運動能が高いにも関わらず、ケラチノサイトの分化マーカー遺伝子発現が更新していることが示唆され、申請者の以前の基盤Ｂ研究で報告した結果とも相反するデータを得ており、今後考察を加え、メカニズム解明したい。また、コロナの影響で、研究分担者のいる北海道大学にＡＦＭを用いた細胞の硬さ検索ができなかった。
日本学術振興会, 基盤研究(B), 新潟大学, 20H03870

Molecular Mechanism and Universality in Collective Invasion of Cancer Cells Induced by Contact Following
Grants-in-Aid for Scientific Research(基盤研究(C))
2017 - 2019
Hisashi HAGA
Ministry of Education, Culture, Sports, Science and Technology, Principal investigator, Competitive research funding

Discovery of the logic that establishes the 3D structure of organisms
科学研究費補助金(新学術領域研究(研究領域提案型))
2015 - 2019
Hisashi HAGA
Ministry of Education, Culture, Sports, Science and Technology, Principal investigator, Competitive research funding

３Ｄ形態ロジックの国際共同研究を加速するバーチャル研究所
科学研究費補助金(新学術領域研究(研究領域提案型))
2015 - 2019
Shigeru KONDO
Ministry of Education, Culture, Sports, Science and Technology, Competitive research funding

3D morphologic
科学研究費補助金(新学術領域研究(研究領域提案型))
2015 - 2019
Shigeru KONDO
Ministry of Education, Culture, Sports, Science and Technology, Competitive research funding

細胞外基質の硬さに誘引される転写調節因子ATF5の活性と浸潤能亢進の機序
科学研究費補助金(基盤研究(C))
2014 - 2016
Hisashi HAGA
High matrix stiffness triggers cancer progression; however, detailed molecular mechanisms of this phenomenon are not clear. Hence, it is necessary to identify transcription factors that contribute to malignant alteration in response to increasing substrate stiffness. In this study, we found that activating transcription factor 5 (ATF5) enhances the invasiveness of cancer cells. In addition, we revealed that ATF5 regulates the expression of genes encoding integrins, which are important for substrate stiffness sensing. Based on these observations, ATF5 possibly drives cancer progression due to stiff matrix. We also examined ATF5 localization on substrates with different rigidity. Matrix rigidity affects ATF5 transport to the nucleus.
文部科学省, 基盤研究(C), 北海道大学, Principal investigator, Competitive research funding, 26430104

がん細胞は自身の生存をかけ放射線域を逃れるべく上皮間葉移行をなしうるか
科学研究費助成事業
01 Apr. 2012 - 31 Mar. 2015
西岡 健, 芳賀 永, 安田 元昭, 武島 嗣英
今年度の実験において我々は5'UTRおよび3'UTR依存性発現調節の候補遺伝子の機能解析を行った。5'UTR結合タンパク質に関してはSRSFファミリーが有望であると考えられた。これらタンパク質はHIF-laあるいはcMYCの5'UTRを挿入したルシフェラーゼリポーターからのタンパク質発現を数倍に活性化することができた。これら候補遺伝子の発現を、マイクロアレイにて比較したところ、予想通り高転移性株では発現が高い傾向が認められた。これらの発現が遺伝子プロモーター領域の配列の違いによるものか否かを判断するため、アレイ解析に用いた細胞のゲノムDNAを出発材料にしてプロモーター領域のシークエンスを行ったところ顕著な塩基置換は認められず、メチル化などのエピジェネティックな変化の解析が今後の課題として提起された。3'UTR依存性発現調節の候補遺伝子としてELAVLファミリータンパク質の1つであるELAVL2の機能解析を行った。ELAVL1はほぼ全ての細胞において多量に発現し主に核局在を示すが、ELAVL2は主に細胞質に局在する。ELAVL2導入細胞株ではELAVL1を導入した細胞よりも、ARE mRNA由来のタンパク質発現レベルが有意に上昇していた。蛍光タンパク質タグを付与したHuRを単独で強制発現させてもELAVL1は核局在を示したが、ELAVL1とELAVL2を同時に発現させた細胞では細胞質局在するELAVL1が認められた。two-hybrid法にて、ELAVL1どうしの結合よりELAVL1-ELAVL2間のほうがより強い結合であることが示された。この結合にはELAVL2のN末端、C末端領域が必要であった。ELAVL1の核から細胞質への局在変化にはELAVL2が大きく関わっていること、ELAVL2の発現量はがん細胞の悪性度と相関することが示唆された。これまで3'UTR依存性の翻訳抑制機構を担うと報告されてきたELAVL1はむしろHIF-1αの翻訳効率を低下させることが示され、従来考えられてきた調節機構はより複雑なものであることが示唆された。
日本学術振興会, 基盤研究(B), 北海道大学, 24390285

Tension-induced conformational changes of actin filaments and their influence on actin binding and intracellular localization of myosin.
Grants-in-Aid for Scientific Research
01 Apr. 2012 - 31 Mar. 2015
UYEDA Taro, YUMURA Shigehiko, HAGA Hisashi, NOGUCHI Taro, ADACHI Taiji
To elucidate the mechanism by which actin filaments perform different functions in vivo, we tested the hypothesis that tension applied to actin filaments increases affinity for myosin II. We were able to estimate the tension applied to actin filaments in amoeba cells. Experimental system to visualize myosin binding to tensed actin filaments in vitro was established, opening an avenue to directly test the hypothesis in vitro in the future. Some progress was also made in attempts to visualize tensed actin filaments in amoeba cells using a FRET-based system, demonstrating that the actin filaments in cells are polymorphic.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), National Institute of Advanced Industrial Science and Technology, 24370069

ゲル基質の軟らかさと粘性を利用した上皮シートの3次元組織構築
科学研究費補助金(新学術領域研究(研究領域提案型))
2014 - 2015
Hisashi HAGA
本研究課題は，ゲル基質を用いて上皮細胞に腸管絨毛のような立体構造（チューリップハット様の構造）を形成させるシステムを構築することを目的とする．研究代表者はこれまでに，上皮細胞をマトリゲル上に播種すると，上皮シートの辺縁部が内側に収縮し，ゲル基質を変形させながら回転運動を行い，絨毛構造を形成することを発見した．本研究では，この現象を組織再生の基礎技術とするために，①上皮シートの辺縁部が収縮する機構，②ゲル基質の粘性がもたらす効果，③シート全体が回転運動する機構の3点に焦点を当てて研究を遂行した．
平成27年度では，交付申請書における研究実施計画に従って，リーダー細胞の出現による形態形成への機序解明と様々な粘性係数をもつ粘性基質の開発を行った．実験の結果，上皮間葉転移（EMT）を誘引する受容体を薬剤阻害してもチューリップハット構造の形成が阻害されることはなかった．リーダー細胞の出現，およびチューリップハット構造の形成にはEMTのシグナル経路は関与しないことが明らかとなった．また，粘性基質の開発については，シリコーンオイルにPDMSを混ぜることで任意の粘性係数を実現することに成功した．粘性基質上に播種した上皮細胞が様々な形の突起構造，管状構造を形成することを発見した．さらに，従来法であるマトリゲルに架橋剤としてゲニピンを混ぜることで，任意の粘性係数をもつ新規のマトリゲル基質を開発した．ゲニピンの濃度を調節し，粘性係数を変えことで任意のサイズの突起構造を形成させることに成功した．
これらの結果は，平成27年度内にScientific Reports誌に原著論文として公開することができた．
文部科学省, 新学術領域研究(研究領域提案型), 北海道大学, Principal investigator, Competitive research funding, 26106702

多数の細胞の力と運動がもたらす管腔構造形成のロジック
科学研究費補助金(新学術領域研究(研究領域提案型))
2013 - 2014
Hisashi HAGA
本研究課題は，上皮細胞の集団が協調して力を出し合い，管腔組織を形成するロジックを明らかにすることを目的とする．研究代表者はこれまでに，上皮細胞（MDCK細胞）をコラーゲンゲルで重層すると，上皮シートの辺縁部が内側に収縮し，シート全体が湾曲しながら折り返されることで管腔構造が形成されることを発見した．本研究では，この現象が生じるロジックを解明するために，①上皮シート端が折り返す機構，②折り返した細胞に追随して後続細胞が集団で運動する機構，③上皮シートが湾曲し間隙が形成される機構の3点に焦点を当てて研究を遂行した．
平成26年度では，交付申請書における研究実施計画に従って，上皮シート辺縁部を取り囲むアクトミオシン束の収縮力発生機構について調べた．とくに，細胞に大きな収縮力をもたらすII型ミオシン調節軽鎖（MRLC）の2重リン酸化機構に着目して実験を行った．具体的には，阻害剤投与，免疫蛍光染色，siRNAによる発現抑制，FRETプローブを用いた蛍光ライブイメージングを行うことで，MRLCの2重リン酸化に寄与するリン酸化酵素（ROCK，ZIP-kinase，MLCK）の働きについて検討した．その結果，MLCKは折り返しには寄与せず，ROCKとZIP-kinaseの寄与が大きいことが明らかとなった．とくに，ZIP-kinaseの働きについてはあまり知られていなかったので，今回の発見は細胞の集団運動を理解する上で意義が大きいといえる．さらに，研究実施計画に従って，MMP-8の分泌と管腔形成との関係についても調べた．MMP-8の阻害剤を投与したところ，管腔形成に大きな影響を及ぼさないことが明らかとなった．
これらの結果は，平成26年度内にPLoS ONE誌に原著論文として公開することができた．
文部科学省, 新学術領域研究(研究領域提案型), 北海道大学, Principal investigator, Competitive research funding, 25127701

動体追跡医科学研究
科学研究費補助金(基盤研究(A))
2009 - 2012
Hiroki SHIRATO, 本間 さと, 玉木 長良, 芳賀 永, 但野 茂, 石川 正純
放射線を軸に、ナノレベルの物理現象から社会的存在としての患者まで生体の動体追跡科学の基盤研究を行った。電子線トラック特性解析から細胞生存率モデルを提案した。DNAの二本鎖切断のうち修復されずに残るものの数がPoisson分布し、それが潜在的致死(PL)損傷であると仮定するNLP(Non-Lethal Probability)モデルによって、照射後の細胞の生存率をより適切に説明できた。細胞への放射線効果の予測を統計学的に行う際には、解析対象を分布値で表現する解析法を導入することで、より正しく記述できることが示唆された。ひと由来がん細胞が軟らかい基盤上の動きを観察したところNF-κBやLOXとの関係がわかり、細胞のゲル器質内への侵潤の3次元的観察系を構築する基礎が整った。マウス体内の各部位における遺伝子発現をリアルタイムに長期間、自由行動中の動物から計測する小動物内の分子の動体追跡技術を開発した。ルシフェラーゼレポーターを用い、体表からの微弱発光レベルの三次元空間における長期間追跡を行うことができ、定量的追跡への土台が整った。サルの脳定位照射・動体追跡照射の実験を可能にするために、準備的検討を行った。大動物の動体追跡実験が可能になると、生理学的検討に使える可能性が高い。ひとがん組織の放射線治療後の腫瘍の変化を定量的に記載し、予測するためのモデルを構築した。ひとがん腫瘤の動体追跡の...
文部科学省, 基盤研究(A), 北海道大学, Coinvestigator not use grants, Competitive research funding, 21249065

基質の軟らかさによって誘引される細胞の協調的集団運動に関する研究
科学研究費補助金(基盤研究(C))
2009 - 2011
Hisashi HAGA, 川端 和重
細胞集団に自発的な協調運動を誘引させるため,コラーゲンゲルを作成し,その上に上皮細胞(MDCK細胞)を培養した.平成22年度では,細胞外基質との接着構造を解析し,リーダー細胞の出現機構について調べた.さらに,細胞間に「力」を伝達するセンサーの探索を行った.(1)細胞-基質間の接着構造の解析これまでの実験結果によって,軟らかいゲル基質上においては,リーダー細胞のみが基質との接着部位にintegrin-β1を発現し,リーダー細胞以外の細胞は別の接着タンパク質を発現していることが示唆されていた.平成22年度では,RT-PCRにより,リーダー細胞以外の細胞における接着構造の解明を目指した.しかし,integrin-β3,β4,β7など幾つか候補が見つかったものの,接着タンパク質の同定には至らなかったので,次年度も継続して実験を行う予定である.(2)リーダー細胞の出現機構の解明これまでの実験結果によって,基質の硬さに伴って上皮-間質転換(EMT)が誘引され,リーダー細胞が出現することが示唆されていた.平成22年度では,MDCK細胞のサブクローニングを行い,発現遺伝子と表現型を調べることでEMTを検証した.その結果,ガラス基盤上でも集団運動を示すサブクローンの獲得に成功した.そのサブクローンは細胞間接着が極めて強固であり,E-cadherinが有意に発現していることが明らかとなった.さら...
文部科学省, 基盤研究(C), 北海道大学, Principal investigator, Competitive research funding, 21570158

力学的応答測定を利用した極微小タンパク質結晶の判別・評価法の開発
科学研究費補助金(挑戦的萌芽研究)
2009 - 2010
Isao TANAKA, 芳賀 永
本研究課題では,タンパク質結晶化初期スクリーニングにおいて析出する極微小結晶様物質の力学的応答特性を,走査型プローブ顕微鏡を用いて測定するための研究開発を行った.前年度までに,走査型プローブ顕微鏡でタンパク質結晶を観察する系を構築し,さらに塩の結晶についても同様の実験系を考案した.本年度は,タンパク質結晶および塩結晶の測定数を増やすことに取り組んだ.タンパク質結晶については,ニワトリ卵白リゾチームと甘味タンパク質ソーマチンについては成功したが,確立した実験系ではかなり高濃度のタンパク質溶液が多量に必要となり,かつ通常の結晶化とは方式が異なるため,既存の結晶化戦略との溝を埋めるような研究が必要とされる.また本課題内で,結晶面の違いによって,力学的性質の差異が示唆されたため,異なる結晶面の特性を比較検討する研究が必要であることが見出された.塩類の結晶について本年度は,前年に成功したNaClと同様の方法によってさまざまな塩類を結晶化させることを試みたが,NaCl以外では測定に適した結晶を得ることはできず,タンパク質と塩類を詳細に比較するためには,異なる方法で結晶を得る必要がある.タンパク質とNaClの結晶の力学的応答を比較した場合,前者のほうが弾性に富むこと,またNaClの結晶は,表面に強い電荷を帯びていることが示唆され,結晶の判別に応用できることが期待された.しかし,タンパク質と...
文部科学省, 挑戦的萌芽研究, 北海道大学, Coinvestigator not use grants, Competitive research funding, 21657026

The secret of radiation-surviving cell : multidisciplinary approach to eradicate cancer
Grants-in-Aid for Scientific Research(基盤研究(B))
2008 - 2010
Takeshi NISHIOKA, 芳賀 永, 安田 元昭, 本間 明宏, 堤香 織, 酒井 正春
Treatment with any cytotoxic agent can trigger surviving cells in a tumor to divide faster than before. This phenomenon is widely recognized as "repopulation". To better clarify the mechanism, gene expression profiling and pathological experiments were performed. A mouse fibrosarcoma cell line, QRsP, was used. Cells were irradiated with 10 Gy. Colony assay and cloning were performed. Six clones were established. cDNA analysis was performed on the clone that showed the largest number of colonies on the 2nd 10 Gy irradiation. Mouse transplantation experiment was then carried out. cDNA analysi...
Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Coinvestigator not use grants, Competitive research funding, 20390319

Mechanical memory effect of cells in colony
Grants-in-Aid for Scientific Research(基盤研究(B))
2006 - 2008
Kazushige KAWABATA, 芳賀 永, 根本 幸児
細胞集団がどのように連携・協同して血管や臓器などのマクロな形態を形成するかその機構を解明することを目的に、細胞に蓄積される力学的記憶効果を調べた。本研究では、走査型プローブ顕微鏡を用いた新たな測定装置を構築し、細胞に力学的変形刺激を加えた場合に細胞内に発生する力の応答を調べた。その結果、細胞の変形パターンによって、その後の細胞の力学的応答が大きく異なり、細胞レベルに力学的な記憶効果があることを明らかにした。
Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Coinvestigator not use grants, Competitive research funding, 18340122

Radiation-induced highly-malignant cancer cells: the mechanism and how to deal with it
Grants-in-Aid for Scientific Research(基盤研究(B))
2006 - 2007
Takeshi NISHIOKA, 安田 元昭, 芳賀 永, 本間 明宏, 堤 香織
Novel function of transcription factor ATF5: blockade of p53-dependent apoptosis induced by irradiation.Purpose: p53-dependent cell death is considered as a predominant mechanism of tumor cell apoptosis induced by ionizing irradiation, and a large number of studies have shown that mutant p53-harboring tumor cells with a p53 gene mutation exhibit radioresistance. However, even tumor cells that express wild-type p53 display various degrees of radiosensitivity to ionizing irradiation. This indicates that there are additional pathways that affect p53-dependent cell death mechanisms. Here we des...
Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Coinvestigator not use grants, Competitive research funding, 18390325

細胞システムにおける「力学平衡」モデルの実証
科学研究費補助金(萌芽研究)
2003 - 2004
Kazushige KAWABATA, 芳賀 永
細胞運動や組織形成などには、基質の伸展刺激や流れずり応力等の力学的刺激が重要な働きをすることが知られている。本研究の目的は、外力に対する細胞の力学的応答を調べることにより、細胞内のアクチンフィラメントネットワークの動的性質を明らかにする、特に、外的刺激に対する力学的な平衡状態(張力ホメオスタシス)の存在およびその性質また分子レベルでの要因を明らかにすることである。本研究により得た結果は以下である。1)弾性シャーレを用いて、生きたマウス繊維芽細胞(NIH-3T3)を伸長もしくは収縮させた時の、細胞のかたさ分布の時間変化を力学SPMを用いて測定した。細胞内のアクチンストレスファイバーに働く張力にも恒常性が存在し、元の状態に戻るために2時間程度の時定数を持つ。2)ストレスファイバーの収縮力の起源であるミオシン調節軽鎖(MRLC ; Myosin Regulatory Light Chain)に結合したリン酸数と張力の応答の関係を調べた。1リン酸化はできるが2リン酸化することが出来ないMRLC(MRLC-T18A)を過剰に発現させた細胞を機械的に伸張させ、その力学的応答をSPMによって測定した。この細胞では細胞内張力ホメオスタシスは起こらない。3)wild-type細胞を伸長もしくは収縮し、リン酸化されたMRLCの細胞内の空間分布を共焦点蛍光顕微鏡で観察した。細胞の伸長直後にストレス...
文部科学省, 萌芽研究, 北海道大学, Coinvestigator not use grants, Competitive research funding, 15650051

ナノ力学プローブ顕微鏡による結合組織の形成過程における力学的制御機構の解明
科学研究費補助金(若手研究(B))
2002 - 2004
Hisashi HAGA
前年度に開発した広域走査が可能な新型の走査型プローブ顕微鏡(WR-SPM)を用いて、上皮細胞が増殖し上皮組織を形成するまでの過程を力学的な見地から観察を行った。これまで市販のSPMでは100ミクロン程度の走査範囲が限界であったが、新たに開発したWR-SPMでは400ミクロンのエリアを走査することが可能となっている。現在までに、数百の細胞からなる上皮細胞のコロニー全体に対する弾性率分布の経時変化測定に成功している。さらに、一細胞レベルにおける細胞内張力のダイナミクスについてのSPM観察を行った。その結果、ストレスファイバーを構成するII型ミオシン調節軽鎖(MRLC)のリン酸化が細胞内張力の発生起源であり、伸長もしくは収縮といった外力が細胞に加わっても、細胞はMRLCのリン酸化レベルを変化させることで、細胞の形態や細胞内張力を安定化させていることが明らかとなった。また、保温装置付きの位相差顕微鏡を用いて、コラーゲンゲル基盤上で培養した上皮細胞が上皮コロニーを形成しながら集団で運動する過程を長時間観察した。その結果、(1)コラーゲン線維の配向性が上皮細胞の集団運動の方向を決定する。(2)ゲル基盤上の上皮細胞には、amoeboid型運動をするfollower細胞と、mesenchymal型運動をするleader細胞が存在し、それらの細胞の役割分担が空間的に制御されることで、上皮細胞は集団で一定方向に効率良く運動し、結合組織の形成を行う。ことなどが明らかとなった。以上、SPMで得られた結果と位相差顕微鏡による長時間観察の結果を比較すると、上皮細胞は組織を形成する過程において上皮コロニー周辺部のleader細胞が牽引力を発生し、その力がコロニー中心部に伝わることでコロニー全体が協調して一定方向に運動することが明らかとなった。
文部科学省, 若手研究(B), 北海道大学, Principal investigator, Competitive research funding, 14780536

Quantitative evaluation of visco-elastic distribution of living cells using scanning probe microscopy
Grants-in-Aid for Scientific Research(基盤研究(C))
2002 - 2003
Yoshihiko HIRAI, 芳賀 永, 川端 和重, 田中 芳雄, 川田 博昭, 菊田 久雄
Understanding cellular migration as an integrated mechanical system requires an experimental investigations on mechanical properties of living cells. Force modulation mode with SPM is proposed as a useful method fur measuring stiffness of living cells with high temporal and spatial resolution. However, in liquid environment, cellular stiffness obtained by force modulation mode is often incredible.To clear this problem, numerical analysis of the 1-dimensional dynamic equation of a-micro cantilever, which concern about the visco-elastic property of the sample and viscosity of the liquid, is c...
Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(C), 大阪府立大学, Coinvestigator not use grants, Competitive research funding, 14550222

生細胞の組織形成過程における力学的制御機構の解明　　　　　　　　　　　　　　　
1996
Competitive research funding

細胞の培養方法、細胞の培養方法を用いたスクリーニング方法、培養装置及び培養キット
Patent right, 石原 誠一郎, 芳賀 永, 石原 すみれ, 国立大学法人北海道大学
特願2022-011768, 28 Jan. 2022
特開2023-110368, 09 Aug. 2023
202303008233677554

ゲルの製造方法及びコラーゲンゲル　　　　　　　　　　　　　　　
Patent right
特願2018-007402, 19 Jan. 2018
特開2019-123845, 25 Jul. 2019