Researcher basic information

• Ph.D., Tokyo Institute of technology

• https://researchmap.jp/read0118370?lang=en

• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200901031272190624
• http://www.ist.hokudai.ac.jp/labo/cell/
• http://cell-c.ist.hokudai.ac.jp/

• 200901031272190624

• 応用物理学一般
• 生物物理学
• バイオナノテクノロジー
• Polymer Science
• Biophysics
• Bionanotechnology

• Life Science, Biophysics
• Nanotechnology/Materials, Applied condensed matter physics
• Natural Science, Biophysics, chemical physics and soft matter physics
• Nanotechnology/Materials, Nanobioscience
• Nanotechnology/Materials, Nanomaterials

• Bachelor's degree program, School of Engineering
• Master's degree program, Graduate School of Information Science and Technology
• Doctoral (PhD) degree program, Graduate School of Information Science and Technology

Research activity information

• Mapping single-cell rheology of ascidian embryos in the cleavage stages using AFM,
  Takahiro Kotani; Tomohiro Matsuo; Megumi Yokobori; Yosuke Tsuboyama; Yuki Miyata; Yuki Fujii; Kaori Kuribayashi-Shigetomi; Takaharu Okajima
  Biophysical Journal, May 2025, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Enhancement of neural crest formation by mechanical force in Xenopus development,
  Toki Kaneshima; Masaki Ogawa; Takayoshi Yamamoto; Yosuke Tsuboyama; Yuki Miyata; Takahiro Kotani; Takaharu Okajima; Tatsuo Michiue
  International Journal of Developmental Biology, 68, 25, 37, Apr. 2024, [Peer-reviewed]
  English, Scientific journal
• Local Intracellular stiffening of ascidian embryo in cleavage developmental stage observed by atomic force microscopy
  Takahiro Kotani; Yuki Miyata; Yosuke Tsuboyama; Yuki Fujii; Takaharu Okajima
  Japanese Journal of Applied Physics, 63, 04SP64, Apr. 2024, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Compressed sensing reconstruction of cell mechanical images obtained from atomic force microscopy
  Yuki Miyata; Feng-Yueh Chan; Takayuki Uchihashi; Takaharu Okajima
  Japanese Journal of Applied Physics, 63, 4, 04SP46, 04SP46, IOP Publishing, Apr. 2024, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal, Abstract
  
  Compressed sensing (CS), a technique in signal processing that reconstructs sparse signals from a limited sampling number, has been valuable in topographic images obtained from atomic force microscopy (AFM). However, how CS is effective in reconstructing AFM mechanical images remains unclear. We investigated the reconstruction of topographic and mechanical images of living cells, such as developing embryos obtained from AFM mapping experiments using CS. The results showed that both topographic and mechanical images of embryonic cells in the different developmental stages were well reconstructed at a spatial resolution higher than the original AFM images. These results suggested that the CS approach enabled the cell mechanical properties, together with cell surface morphology, using AFM mapping measurements to be faster than the conventional AFM methods without reducing the spatial resolution.
• Mechanical properties of epithelial cells in domes investigated using atomic force microscopy
  K. Shigemura; K. Kuribayashi-Shigetomi; R. Tanaka; H. Yamasaki; T. Okajima
  Frontiers in Cell and Developmental Biology, 11, 1245296, Oct. 2023, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Atomic force microscopy for investigating cell and tissue mechanics as heterogeneous and hierarchical materials, Journal of Biomechanical Science and Engineering
  T. Okajima; K. Kuribayashi-Shigetomi
  Journal of Biomechanical Science and Engineering, Oct. 2023, [Peer-reviewed], [Invited], [Lead author, Corresponding author]
  English, Scientific journal
• Pathogenic Roles of Cardiac Fibroblasts in Pediatric Dilated Cardiomyopathy.
  Hirofumi Tsuru; Chika Yoshihara; Hidehiro Suginobe; Mizuki Matsumoto; Yoichiro Ishii; Jun Narita; Ryo Ishii; Renjie Wang; Atsuko Ueyama; Kazutoshi Ueda; Masaki Hirose; Kazuhisa Hashimoto; Hiroki Nagano; Ryosuke Tanaka; Takaharu Okajima; Keiichi Ozono; Hidekazu Ishida
  Journal of the American Heart Association, e029676, 22 Jun. 2023, [International Magazine]
  English, Scientific journal, Background Dilated cardiomyopathy (DCM) is a major cause of heart failure in children. Despite intensive genetic analyses, pathogenic gene variants have not been identified in most patients with DCM, which suggests that cardiomyocytes are not solely responsible for DCM. Cardiac fibroblasts (CFs) are the most abundant cell type in the heart. They have several roles in maintaining cardiac function; however, the pathological role of CFs in DCM remains unknown. Methods and Results Four primary cultured CF cell lines were established from pediatric patients with DCM and compared with 3 CF lines from healthy controls. There were no significant differences in cellular proliferation, adhesion, migration, apoptosis, or myofibroblast activation between DCM CFs compared with healthy CFs. Atomic force microscopy revealed that cellular stiffness, fluidity, and viscosity were not significantly changed in DCM CFs. However, when DCM CFs were cocultured with healthy cardiomyocytes, they deteriorated the contractile and diastolic functions of cardiomyocytes. RNA sequencing revealed markedly different comprehensive gene expression profiles in DCM CFs compared with healthy CFs. Several humoral factors and the extracellular matrix were significantly upregulated or downregulated in DCM CFs. The pathway analysis revealed that extracellular matrix receptor interactions, focal adhesion signaling, Hippo signaling, and transforming growth factor-β signaling pathways were significantly affected in DCM CFs. In contrast, single-cell RNA sequencing revealed that there was no specific subpopulation in the DCM CFs that contributed to the alterations in gene expression. Conclusions Although cellular physiological behavior was not altered in DCM CFs, they deteriorated the contractile and diastolic functions of healthy cardiomyocytes through humoral factors and direct cell-cell contact.
• Atomic force microscopy identifies the alteration of rheological properties of the cardiac fibroblasts in idiopathic restrictive cardiomyopathy.
  Mizuki Matsumoto; Hirofumi Tsuru; Hidehiro Suginobe; Jun Narita; Ryo Ishii; Masaki Hirose; Kazuhisa Hashimoto; Renjie Wang; Chika Yoshihara; Atsuko Ueyama; Ryosuke Tanaka; Keiichi Ozono; Takaharu Okajima; Hidekazu Ishida
  PloS one, 17, 9, e0275296, Sep. 2022, [Corresponding author], [International Magazine]
  English, Scientific journal, Restrictive cardiomyopathy (RCM) is a rare disease characterized by increased ventricular stiffness and preserved ventricular contraction. Various sarcomere gene variants are known to cause RCM; however, more than a half of patients do not harbor such pathogenic variants. We recently demonstrated that cardiac fibroblasts (CFs) play important roles in inhibiting the diastolic function of cardiomyocytes via humoral factors and direct cell-cell contact regardless of sarcomere gene mutations. However, the mechanical properties of CFs that are crucial for intercellular communication and the cardiomyocyte microenvironment remain less understood. In this study, we evaluated the rheological properties of CFs derived from pediatric patients with RCM and healthy control CFs via atomic force microscopy. Then, we estimated the cellular modulus scale factor related to the cell stiffness, fluidity, and Newtonian viscosity of single cells based on the single power-law rheology model and analyzed the comprehensive gene expression profiles via RNA-sequencing. RCM-derived CFs showed significantly higher stiffness and viscosity and lower fluidity compared to healthy control CFs. Furthermore, RNA-sequencing revealed that the signaling pathways associated with cytoskeleton elements were affected in RCM CFs; specifically, cytoskeletal actin-associated genes (ACTN1, ACTA2, and PALLD) were highly expressed in RCM CFs, whereas several tubulin genes (TUBB3, TUBB, TUBA1C, and TUBA1B) were down-regulated. These results implies that the signaling pathways associated with cytoskeletal elements alter the rheological properties of RCM CFs, particularly those related to CF-cardiomyocyte interactions, thereby leading to diastolic cardiac dysfunction in RCM.
• 原子間力顕微鏡による発生胚皮質領域の力学測定、膜、47、269-272(2022).
  岡嶋孝治
  膜、47、269-272(2022)., 47, 269, 272, 2022, [Peer-reviewed], [Invited]
  Japanese
• 、原子間力顕微鏡：多細胞系の力学物性計測の現状、62、159-164(2022).[book]
  岡嶋孝治
  生物物理（解説）, 62, 159, 164, 2022, [Peer-reviewed], [Lead author, Last author, Corresponding author]
  Japanese
• Pharmacological Alteration of Cellular Mechanical Properties in Pulmonary Arterial Smooth Muscle Cells of Idiopathic Pulmonary Arterial Hypertension
  Shinichi Katsuragi; Nao Tatsumi; Mizuki Matsumoto; Jun Narita; Ryo Ishii; Hidehiro Suginobe; Hirofumi Tsuru; Renjie Wang; Shigetoyo Kogaki; Ryosuke Tanaka; Keiichi Ozono; Takaharu Okajima; Hidekazu Ishida
  Cardiology Research, 12, 4, 231, 237, Elmer Press, Inc., Aug. 2021, [Peer-reviewed], [Corresponding author], [International Magazine]
  English, Scientific journal, Background: Idiopathic pulmonary arterial hypertension (IPAH) is a progressive disease caused by vascular remodeling of the pulmonary arteries with elevated pulmonary vascular resistance. Recently, various pulmonary vasodilator drugs have become available in the clinical field, and have dramatically ameliorated the prognosis of IPAH. However, little is known about how the mechanical properties of pulmonary arterial smooth muscle cells (PASMCs) are altered under drug supplementation. Methods: Atomic force microscopy (AFM) was used to investigate the mechanical properties of PASMCs derived from a patient with IPAH (PAH-PASMCs) and a healthy control (N-PASMCs) which received the supplementation of clinically used drugs for IPAH: sildenafil, macitentan, and riociguat. Results: PASMCs derived from PAH-PASMCs were stiffer than those derived from N-PASMCs. With sildenafil treatment, the apparent Young's modulus (E 0) of cells significantly decreased in PAH-PASMCs but remained unchanged in N-PASMCs. The decrease in E 0 of PAH-PASMCs was also observed in macitentan and riociguat treatment. The stress relaxation AFM revealed that the decrease in E 0 of PAH-PASMCs resulted from a decrease in the cell elastic modulus and/or increase in cell fluidity. The combination treatment of macitentan and riociguat showed an additive effect on cell mechanical properties, implying that this clinically accepted combination therapy for IPAH influences the intracellular mechanical components. Conclusions: Pulmonary vasodilator drugs affect the mechanical properties of PAH-PASMCs, and there exists a mechanical effect of combination treatment on PAH-PASMCs.
• Spatiotemporal dynamics of single cell stiffness in the early developing ascidian chordate embryo
  Y. Fujii; W. C. Koizumi; T. Imai; M. Yokobori; T. Matsuo; K. Oka; K. Hotta; T. Okajima
  Communications Biology, 4, 1, 341, 341, Springer Science and Business Media LLC, 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
  English, Scientific journal, During the developmental processes of embryos, cells undergo massive deformation and division that are regulated by mechanical cues. However, little is known about how embryonic cells change their mechanical properties during different cleavage stages. Here, using atomic force microscopy, we investigated the stiffness of cells in ascidian embryos from the fertilised egg to the stage before gastrulation. In both animal and vegetal hemispheres, we observed a Rho kinase (ROCK)-independent cell stiffening that the cell stiffness exhibited a remarkable increase at the timing of cell division where cortical actin filaments were organized. Furthermore, in the vegetal hemisphere, we observed another mechanical behaviour, i.e., a ROCK-associated cell stiffening, which was retained even after cell division or occurred without division and propagated sequentially toward adjacent cells, displaying a characteristic cell-to-cell mechanical variation. The results indicate that the mechanical properties of embryonic cells are regulated at the single cell level in different germ layers.
• Measuring viscoelasticity of soft biological samples using atomic force microscopy
  Yuri M. Efremov; Takaharu Okajima; Arvind Raman
  Soft Matter, 16, 64, 81, 2020, [Peer-reviewed]
  English, Scientific journal
• Stiffness of brewers’ yeast under ethanol stress investigated by atomic force microscopy
  K. Toyota, R. Tanaka, T. Okajima
  Japanese Journal of Applied Physics, 59, SN1005, 2020, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Relationship between rheological properties and actin filaments of single cells investigated by atomic force microscopy
  R. Tanaka, M. Sawano, Y. Fujii, K. Kuribayashi-Shigetomi, A. Subagyo, K. Sueoka, T. Okajima*
  Japanese Journal of Applied Physics, 59, SN1010, 2020, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Spontaneous Spatial Correlation of Elastic Modulus in Jammed Epithelial Monolayers Observed by AFM.
  Yuki Fujii; Yuki Ochi; Masahiro Tuchiya; Mihoko Kajita; Yasuyuki Fujita; Yukitaka Ishimoto; Takaharu Okajima
  Biophysical journal, 116, 6, 1152, 1158, 19 Mar. 2019, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
  English, Scientific journal, For isolated single cells on a substrate, the intracellular stiffness, which is often measured as the Young's modulus, E, by atomic force microscopy (AFM), depends on the substrate rigidity. However, little is known about how the E of cells is influenced by the surrounding cells in a cell population system in which cells physically and tightly contact adjacent cells. In this study, we investigated the spatial heterogeneities of E in a jammed epithelial monolayer in which cell migration was highly inhibited, allowing us to precisely measure the spatial distribution of E in large-scale regions by AFM. The AFM measurements showed that E can be characterized using two spatial correlation lengths: the shorter correlation length, lS, is within the single cell size, whereas the longer correlation length, lL, is longer than the distance between adjacent cells and corresponds to the intercellular correlation of E. We found that lL decreased significantly when the actin filaments were disrupted or calcium ions were chelated using chemical treatments, and the decreased lL recovered to the value in the control condition after the treatments were washed out. Moreover, we found that lL decreased significantly when E-cadherin was knocked down. These results indicate that the observed long-range correlation of E is not fixed within the jammed state but inherently arises from the formation of a large-scale actin filament structure via E-cadherin-dependent cell-cell junctions.
• Cricket tympanal organ revisited: morphology, development, and possible functions of the adult-specific chitin core beneath the anterior tympanal membrane
  H. Nishino; M. Domae; T. Takanashi; T. Okajima
  Cell and Tissue Research, 377, 2, 1, 22, Springer Science and Business Media LLC, 2019, [Peer-reviewed]
  English, Scientific journal
• Calibrating the Young’s modulus of soft materials with surface tilt angle measured by atomic force microscopy
  Y. Fujii; T. Okajima
  AIP Advances, 9, 015028, 2019, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Fascin in lamellipodia contributes to cell elasticity by controlling the orientation of filamentous actin
  M. Tanaka; Y. Fujii; K. Hirano; T. Higaki; A. Nagasaki; R. Ishikawa; T. Okajima; K. Katoh
  Genes to Cells, 24, 3, 202, 213, 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Fascin, an actin-bundling protein, is present in the filopodia and lamellipodia of growth cones. However, few studies have examined lamellipodial fascin because it is difficult to observe. In this study, we evaluated lamellipodial fascin. We visualized the actin meshwork of lamellipodia in live growth cones by super-resolution microscopy. Fascin was colocalized with the actin meshwork in lamellipodia. Ser39 of fascin is a well-known phosphorylation site that controls the binding of fascin to actin filaments. Fluorescence recovery after photobleaching experiments with confocal microscopy showed that binding of fascin was controlled by phosphorylation of Ser39 in lamellipodia. Moreover, TPA, an agonist of protein kinase C, induced phosphorylation of fascin and dissociation from actin filaments in lamellipodia. Time series images showed that dissociation of fascin from the actin meshwork was induced by TPA. As fascin dissociated from actin filaments, the orientation of the actin filaments became parallel to the leading edge. The angle of actin filaments against the leading edge was changed from 73° to 15°. This decreased the elasticity of the lamellipodia by 40%, as measured by atomic force microscopy. These data suggest that actin bundles made by fascin contribute to elasticity of the growth cone.
• Visualising the dynamics of live pancreatic microtumours self-organised through cell-in-cell invasion
  Y. Miyatake; K. Kuribayashi-Shigetomi; Y. Ohta; S. Ikeshita; A. Subagyo; K. Sueoka; A. Kakugo; M. Amano; T. Takahashi; T. Okajima; M. Kasahara
  Scientific Reports, 8, 14054, 2018, [Peer-reviewed]
  English, Scientific journal
• Origami-based self-folding of co-cultured NIH/3T3 and HepG2 cells into 3D microstructure
  Q. He; T. Okajima; H. Onoe; A. Subagyo; K. Sueoka; K. Kuribayashi-Shigetomi
  Scientific Reports, 8, 1, 4556, Springer Science and Business Media LLC, 2018, [Peer-reviewed]
  English, Scientific journal
• Regulation of Neuritogenesis in Hippocampal Neurons using Stiffness of Extracellular Microenvironment
  A. Tanaka; Y. Fujii; N. Kasai; T. Okajima; H. Nakashima
  PLOS ONE, 13, 2, e019192, 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, The mechanosensitivity of neurons in the central nervous system (CNS) is an interesting issue as regards understanding neuronal development and designing compliant materials as neural interfaces between neurons and external devices for treating CNS injuries and disorders. Although neurite initiation from a cell body is known to be the first step towards forming a functional nervous network during development or regeneration, less is known about how the mechanical properties of the extracellular microenvironment affect neuritogenesis. Here, we investigated the filamentous actin (F-actin) cytoskeletal structures of neurons, which are a key factor in neuritogenesis, on gel substrates with a stiffness-controlled substrate, to reveal the relationship between substrate stiffness and neuritogenesis. We found that neuritogenesis was significantly suppressed on a gel substrate with an elastic modulus higher than the stiffness of in vivo brain. Fluorescent images of the F-actin cytoskeletal structures showed that the F-actin organization depended on the substrate stiffness. Circumferential actin meshworks and arcs were formed at the edge of the cell body on the stiff gel substrates unlike with soft substrates. The suppression of F-actin cytoskeleton formation improved neuritogenesis. The results indicate that the organization of neuronal F-actin cytoskeletons is strongly regulated by the mechanical properties of the surrounding environment, and the mechanically-induced F-actin cytoskeletons regulate neuritogenesis.
• Temporal Variation in Single-Cell Power-Law Rheology Spans the Ensemble Variation of Cell Population
  PingGen Cai; Ryosuke Takahashi; Kaori Kuribayashi-Shigetomi; Agus Subagyo; Kazuhisa Sueoka; John M. Maloney; Krystyn J. Van Vliet; Takaharu Okajima
  Biophysical Journal, 113, 3, 671, 678, Aug. 2017, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Mechanical properties of paraformaldehyde‑treated individual cells investigated by atomic force microscopy and scanning ion conductance microscopy
  S.‐O. Kim; J. Kim; T. Okajima; N.‐J. Cho
  Nano Convergence, 4, 5, 2017, [Peer-reviewed], [Corresponding author]
  English, Scientific journal
• Comparison between power-law rheological parameters of living cells in frequency and time domains measured by atomic force microscopy
  Ryosuke Takahashi; Takaharu Okajima
  JAPANESE JOURNAL OF APPLIED PHYSICS, 55, 8, 08NB22, Aug. 2016, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Mapping power-law rheology of living cells using multi-frequency force modulation atomic force microscopy
  Ryosuke Takahashi; Takaharu Okajima
  APPLIED PHYSICS LETTERS, 107, 17, Oct. 2015, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Time-lapse imaging of morphological changes in a single neuron during the early stages of apoptosis using scanning ion conductance microscopy
  Aya Tanaka; Ryosuke Tanaka; Nahoko Kasai; Shingo Tsukada; Takaharu Okajima; Koji Sumitomo
  JOURNAL OF STRUCTURAL BIOLOGY, 191, 1, 32, 38, Jul. 2015, [Peer-reviewed]
  English, Scientific journal
• Precision of cell-to-cell variation in power-law rheology characterized by atomic force microscopy
  PingGen Cai; Takaharu Okajima
  JAPANESE JOURNAL OF APPLIED PHYSICS, 54, 3, Mar. 2015, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Atomic force microscopy for mapping mechanical property of the whole cell assembly
  Ryosuke Tanaka; Yuki Fujii; Junpei Kikkawa; Kaori Kuribayashi-Shigetomi; Agus Subagyo; Kazuhisa Sueoka; Takaharu Okajima
  2014 International Symposium on Micro-NanoMechatronics and Human Science, MHS 2014, Institute of Electrical and Electronics Engineers Inc., 09 Jan. 2015
  English, International conference proceedings
• Atomic Force Microscopy: Imaging and Rheology of Living Cells
  Takaharu Okajima
  Nano/Micro Science and Technology in Biorheology, 2015, [Invited]
• High-throughput Measurements of Single Cell Rheology by Atomic Force Microscopy
  High-throughput Measurements of Single Cell Rheology by; Atomic Force Microscopy; Kaori Kuribayashi-Shigetomi; Ryosuke Takahashi; Agus Subagyo; Kazuhisa Sueoka; Takaharu Okajima
  Hyper Bio Assembler for 3D Cellular Systems, 57, 67, 2015, [Last author, Corresponding author]
  English
• Filamin acts as a key regulator in epithelial defence against transformed cells
  Mihoko Kajita; Kaoru Sugimura; Atsuko Ohoka; Jemima Burden; Hitomi Suganuma; Masaya Ikegawa; Takashi Shimada; Tetsuya Kitamura; Masanobu Shindoh; Susumu Ishikawa; Sayaka Yamamoto; Sayaka Saitoh; Yuta Yako; Ryosuke Takahashi; Takaharu Okajima; Junichi Kikuta; Yumiko Maijima; Masaru Ishii; Masazumi Tada; Yasuyuki Fujita
  NATURE COMMUNICATIONS, 5, Jul. 2014, [Peer-reviewed]
  English, Scientific journal
• Atomic force microscopy measurements of mechanical properties of single cells patterned by microcontact printing
  Ryosuke Takahashi; Satoshi Ichikawa; Agus Subagyo; Kazuhisa Sueoka; Takaharu Okajima
  ADVANCED ROBOTICS, 28, 7, 449, 455, Apr. 2014, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Quantifying cell-to-cell variation in power-law rheology
  Pinggen Cai; Yusuke Mizutani; Masahiro Tsuchiya; John M. Maloney; Ben Fabry; Krystyn J. Van Vliet; Takaharu Okajima
  Biophysical Journal, 105, 5, 1093, 1102, 03 Sep. 2013, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• Nanoscale fluctuations on epithelial cell surfaces investigated by scanning ion conductance microscopy
  Yusuke Mizutani; Myung-Hoon Choi; Sang-Joon Cho; Takaharu Okajima
  APPLIED PHYSICS LETTERS, 102, 17, Apr. 2013, [Peer-reviewed], [Last author, Corresponding author]
  English, Scientific journal
• High-throughput measurements of cell mechanics using atomic force microscopy with micro-patterned substrates.
  Ryosuke Takahashi; Kaori Kuribayashi-Shigetomi; Masahiro Tsuchiya; Agus Subagyo; Kazuhisa Sueoka; Takaharu Okajima
  International Symposium on Micro-NanoMechatronics and Human Science, MHS 2013, Nagoya, Japan, November 10-13, 2013, 1, 3, 2013, [Peer-reviewed]
  International conference proceedings
• Effect of isoproterenol on local contractile behaviors of rat cardiomyocytes measured by atomic force microscopy
  Yusuke Mizutani; Koichi Kawahara; Takaharu Okajima
  Current Pharmaceutical Biotechnology, 13, 14, 2599, 2603, Bentham Science Publishers B.V., 2012, [Peer-reviewed]
  English, Scientific journal
• Atomic force microscopy for the examination of single cell rheology
  Takaharu Okajima
  Current Pharmaceutical Biotechnology, 13, 14, 2623, 2631, Bentham Science Publishers B.V., 2012, [Peer-reviewed]
  English
• Direct observation of dynamic force propagation between focal adhesions of cells on microposts by atomic force microscopy
  Akinori Okada; Yusuke Mizutani; Agus Subagyo; Hirotaka Hosoi; Motonori Nakamura; Kazuhisa Sueoka; Koichi Kawahara; Takaharu Okajima
  APPLIED PHYSICS LETTERS, 99, 26, 263703, Dec. 2011, [Peer-reviewed]
  English, Scientific journal
• Negative-feedback regulation of ATP release: ATP release from cardiomyocytes is strictly regulated during ischemia
  Kunugi, Satohiko; Iwabuchi, Sadahiro; Matsuyama, Daisuke; Okajima, Takaharu; Kawahara, Koichi
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 416, 3-4, 409, 415, Dec. 2011, [Peer-reviewed]
  English, Scientific journal
• Rheological Properties of Growth-Arrested Fibroblast Cells under Serum Starvation Measured by Atomic Force Microscopy
  Atsushi Miyaoka; Yusuke Mizutani; Masahiro Tsuchiya; Koichi Kawahara; Takaharu Okajima
  JAPANESE JOURNAL OF APPLIED PHYSICS, 50, 8, 08LB16, Aug. 2011, [Peer-reviewed]
  English, Scientific journal
• Artificial polymeric receptors on the cell surface promote the efficient cellular uptake of quantum dots
  Kenichi Niikura; Katsuyuki Nambara; Takaharu Okajima; Ryosuke Kamitani; Shin Aoki; Yasutaka Matsuo; Kuniharu Ijiro
  ORGANIC & BIOMOLECULAR CHEMISTRY, 9, 16, 5787, 5792, 2011, [Peer-reviewed]
  English, Scientific journal
• Influence of Hydrophobic Structures on the Plasma Membrane Permeability of Lipidlike Molecules
  Kenichi Niikura; Katsuyuki Nambara; Takaharu Okajima; Yasutaka Matsuo; Kuniharu Ijiro
  LANGMUIR, 26, 12, 9170, 9175, Jun. 2010, [Peer-reviewed]
  English, Scientific journal
• マイクロピラー基板上に培養した生細胞のAFMナノ力学測定
  岡田 晃典; 中村 基訓; アグス スバギョ; 細井 浩貴; 末岡 和久; 水谷 裕輔; 河原 剛一; 岡嶋 孝治
  応用物理学会学術講演会講演予稿集, 2010.1, 2673, 2673, 公益社団法人 応用物理学会, 03 Mar. 2010
  Japanese
• Statistics of Single Cell Mechanics Investigated by Atomic Force Microscopy
  Hiratsuka; Y. Mizutani; P.G. Cai; M. Tsuchiya; H. Tokumoto; K. Kawahara; T. Okajima
  MRS Spring Meeting Symposium U proceedings, 9999, 2010, [Peer-reviewed]
• Power-Law Stress and Creep Relaxations of Single Cells Measured by Colloidal Probe Atomic Force Microscopy
  Shinichiro Hiratsuka; Yusuke Mizutani; Akitoshi Toda; Norichika Fukushima; Koichi Kawahara; Hiroshi Tokumoto; Takaharu Okajima
  JAPANESE JOURNAL OF APPLIED PHYSICS, 48, 8, 08JB14-4, Aug. 2009, [Peer-reviewed]
  English, Scientific journal
• The number distribution of complex shear modulus of single cells measured by atomic force microscopy
  Shinichiro Hiratsuka; Yusuke Mizutani; Masahiro Tsuchiya; Koichi Kawahara; Hiroshi Tokumoto; Takaharu Okajima
  ULTRAMICROSCOPY, 109, 8, 937, 941, Jul. 2009, [Peer-reviewed]
  English, Scientific journal
• Design of Cell-Surface-Retained Polymers for Artificial Ligand Display
  Ryosuke Kamitani; Kenichi Niikura; Takaharu Okajima; Yasutaka Matsuo; Kuniharu Ijiro
  CHEMBIOCHEM, 10, 2, 230, 233, Jan. 2009, [Peer-reviewed]
  English, Scientific journal
• Localized yielding around crack tips of double-network gels(a)
  Yoshimi Tanaka; Yasunori Kawauchi; Takayuki Kurokawa; Hidemitsu Furukawa; Takaharu Okajima; Jian Ping Gong
  MACROMOLECULAR RAPID COMMUNICATIONS, 29, 18, 1514, 1520, Sep. 2008, [Peer-reviewed]
  English, Scientific journal
• Elasticity of living cells on a microarray during the early stages of adhesion measured by atomic force microscopy
  Yusuke Mizutani; Masahiro Tsuchiya; Shinichiro Hiratsuka; Koichi Kawahara; Hiroshi Tokumot; Takaharu Okajima
  JAPANESE JOURNAL OF APPLIED PHYSICS, 47, 7, 6177, 6180, Jul. 2008, [Peer-reviewed]
  English, Scientific journal
• Affinity of functional groups for membrane surfaces: Implications for physically irreversible fouling
  Hiroshi Yamamura; Katsuki Kimura; Takaharu Okajima; Hiroshi Tokumoto; Yoshimasa Watanabe
  ENVIRONMENTAL SCIENCE & TECHNOLOGY, 42, 14, 5310, 5315, Jul. 2008, [Peer-reviewed]
  English, Scientific journal
• Observation of the three-dimensional structure of actin bundles formed with polycations
  Kazuhiro Shikinaka; Hyuckjoon Kwon; Akira Kakugo; Hidemitsu Furukawa; Yoshihito Sada; Jian Ping Gong; Yoshitaka Aoyama; Hideo Nishioka; Hiroshi Jinnai; Takaharu Okajima
  BIOMACROMOLECULES, 9, 2, 537, 542, Feb. 2008, [Peer-reviewed]
  English, Scientific journal
• Nanorheology of living cells investigated by atomic force microscopy
  T. Okajima; H. Tokumoto
  Journal of the society of rheology, 36, 81, 86, 2008, [Lead author]
  Japanese
• Stress relaxation measurement of fibroblast cells with atomic force microscopy
  Takaharu Okajima; Masaru Tanaka; Shusaku Tsukiyama; Tsubasa Kadowaki; Sadaaki Yamamoto; Masatsugu Shimomura; Hiroshi Tokumot
  JAPANESE JOURNAL OF APPLIED PHYSICS PART 1-REGULAR PAPERS BRIEF COMMUNICATIONS & REVIEW PAPERS, 46, 8B, 5552, 5555, Aug. 2007, [Peer-reviewed]
  English, Scientific journal
• Actin network formation by unidirectional polycation diffusion
  Hyuck Joon Kwon; Akira Kakugo; Takehiro Ura; Takaharu Okajima; Yoshimi Tanaka; Hidemitsu Furukawa; Yoshihito Osada; Jian Ping Gong
  LANGMUIR, 23, 11, 6257, 6262, May 2007, [Peer-reviewed]
  English, Scientific journal
• Force spectroscopy on single polymer incorporated into polymer gels
  Takaharu Okajima; Xiang-Ming Tao; Hiroaki Azehara; Hiroshi Tokumoto
  JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY, 7, 3, 790, 795, Mar. 2007, [Peer-reviewed]
  English, Scientific journal
• DNA microstructure based on self-assembly of 4-sticky-end holiday junctions in aqueous solution
  Hiroaki Kii; Takuya Takagi; Akira Sasaki; Takaharu Okajima; Masataka Kinjo
  JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY, 7, 3, 726, 729, Mar. 2007, [Peer-reviewed]
  English, Scientific journal
• Stress relaxation of HepG2 cells measured by atomic force microscopy
  T. Okajima; M. Tanaka; S. Tsukiyama; T. Kadowaki; S. Yamamoto; M. Shimomura; H. Tokumoto
  NANOTECHNOLOGY, 18, 8, 084010, Feb. 2007, [Peer-reviewed]
  English, Scientific journal
• Dynamics of a partially stretched protein molecule studied using an atomic force microscope
  Takaharu Okajima; Hideo Arakawa; Mohammad; Taufiq Alam; Hiroshi Sekiguchi; Atsushi Ikai
  Biophysical Chemistry, 107, 51, 61, 2004, [Peer-reviewed], [Lead author, Corresponding author]
  English, Scientific journal
• Frequency shift feedback imaging in liquid for biological molecules
  Hiroshi Sekiguchi; Takaharu Okajima; Hideo Arakawa; Sumihiro Maeda; Akihiko Takashima; Atsushi Ikai
  Applied Surface Science, 210, 61, 67, 2003, [Peer-reviewed]
  English
• Nano-mechanical methods in biochemistry using atomic force microscopy
  Ikai, A; Afrin, R; Sekiguchi, H; Okajima, T; Alam, M.T; Nishida, S
  Current Protein and Peptide Science, 4, 2003, [Peer-reviewed]
  English
• Self-oscillation technique for AFM in liquids
  Takaharu Okajima; Hiroshi Sekiguchi; Hideo Arakawa; Atsushi Ikai
  Applied Surface Science, 210, 68, 72, 2003, [Peer-reviewed], [Lead author, Corresponding author]
  English, Scientific journal
• Non-destructive force measurement in liquid using atomic force microscope
  Hiroshi Sekiguchi; Hideo Arakawa; Takaharu Okajima; Atsushi Ikai
  Applied Surface Science, 188, 489, 2002
  English
• Volume Phase Transition in Neutral Copolymer Gels
  Takaharu Okajima; Shunsuke Hirotsu
  Transactions of the Materials Research Society(!{ Japan, 2001, [Peer-reviewed]
  English
• Use of AFM for imaging and measurement of the mechanical properties of light-convertible organelles in plants
  Takafumi Yamada; Hideo Arakawa; Takaharu Okajima; Takayoshi Shimada; Atsushi Ikai
  Ultramicroscopy, 91, 261, 268, 2001, [Peer-reviewed]
  English
• Discontinuous Crossover between Fast and Slow Kinetics at the Volume Phase Transition in Poly-N-isopropylacrylamide Gels.
  Okajima Takaharu; Harada Ichiro; Nishio Kazufumi; Hirotsu Shunsuke
  Japanese Journal of Applied Physics, 39, 8, L875, L877, The Japan Society of Applied Physics, 2000
  English, The kinetics of the volume phase transition in N-isopropylacrylamide gels has been studied as a function of crosslinker concentration. The shrinking kinetics at the transition is extremely slow in gels with a standard composition which have been used widely in various experiments. A discontinuous crossover from slow to much faster kinetics were observed in both high- and low-crosslinker-concentration regions, where the characteristic time of the shrinking process changes abruptly by two to four orders of magnitude with a minute change of the crosslinker concentration. In spite of these marked changes in the kinetics, no anomaly was observed in the degree of equilibrium swelling in these regions. A mechanism leading to sudden changes in kinetics is discussed in terms of an inhomogeneous network structure which is dependent on crosslink density.
• Study of shear force between glass microprobe and mica surface under controlled humidity
  T Okajima; S Hirotsu
  Applied Physics Letters, 71, 545, 547, 1997, [Peer-reviewed], [Lead author, Corresponding author]
  English
• Brillouin scattering study of the volume phase transition in poly-N-isopropylacrylamide gels
  Shunsuke Hirotsu; Ikuo Yamamoto; Atsushi Matsuo; Takaharu Okajima; Hidemitsu Furukawa; Tatsuyuki Yamamoto
  Journal of the Physical Society of Japan, 64, 8, 2898, 2907, Physical Society of Japan, 1995
  English, Scientific journal
• Change in molecular orientation during thin film growth by evaporation of copolymer of vinylidene fluoride (80%) and tetrafluoroethylene (20%)
  Takaharu Okajima; Kunisuke Maki
  Japanese Journal of Applied Physics, 30, L2055, 1991, [Peer-reviewed]
  English

• Nanoscale Cell Membrane Fluctuations Measured by Scanning Ion Conductance Microscopy
  Yusuke Mizutani; Zen Ishikura; Myung-Hoon Choi; Sang-Joon Cho; Takaharu Okajima, BIOPHYSICAL JOURNAL, 104, 2, 317A, 317A, Jan. 2013, [Peer-reviewed]
  English, Summary international conference
• OS1103 Mechanical properties of living cells in transient-state by atomic force microscopy
  MIZUTANI Yusuke; PINGGEN Cai; TSUCHIYA Masahiro; OKAJIMA Takaharu, M&M材料力学カンファレンス, 2012, "OS1103, 1"-"OS1103-2", 22 Sep. 2012
  Mechanical measurements of single cells are crucial for understanding various cell behaviors. The viscoelastic properties of a number of rat fibroblast cells in the process of transformations such as growth (Phase II), senescence (Phase III) and immortalization (IM) were investigated by atomic force microscopy (AFM) combining with a cell microarray technique. The complex shear modulus of cells as a function of frequency was fitted to a power-law model, consisting of a single power-law function in addition to the Newtonian viscosity. Both the mean value and standard deviation of the power-law exponent a strongly depended on the cell phases. As a result, the power-law behaviors of cells were changed in the process of transformation. In addition, the behaviors were strongly dependent on F-actin microfilaments., The Japan Society of Mechanical Engineers, Japanese
• 1101 Spontaneously Beating Cardiomyocytes Investigated by AFM
  MIZUTANI Yusuke; TSUCHIYA Masahiro; KAWAHARA Koichi; OKAJIMA Takaharu, バイオエンジニアリング講演会講演論文集, 2009, 22, 187, 187, 08 Jan. 2010
  The Japan Society of Mechanical Engineers, Japanese
• 25pPSB-58 Measurement of the Diffusion Process of Living Cell by Fluorescence Correlation Spectroscopy
  Wagatsuma K.; Niikura K.; Kamitani R.; Haruna Y.; Mizutani Y.; Tokumoto H.; Kawahara K.; Okajima T., Meeting abstracts of the Physical Society of Japan, 63, 1, 384, 384, 29 Feb. 2008
  The Physical Society of Japan (JPS), Japanese
• 20pPSA-44 Soft & Wet Matter With Ultra Toughness (2) : Necking Phenomenon in DN gels
  Kawauchi Yasunori; Tanaka Yoshimi; Furukawa Hidemitsu; Okajima Takaharu; Na Yang-Ho; Kurokawa Takayuki; Gong Jian Ping; Osada Yoshihito, Meeting abstracts of the Physical Society of Japan, 62, 1, 366, 366, 28 Feb. 2007
  The Physical Society of Japan (JPS), Japanese
• 18aTC-8 Measurement of Mechanical Relaxation of Living Cells by Atomic Force Microscopy
  Okajima T.; Tanaka M.; Tsukiyama S.; Kadowaki T.; Yamamoto S.; Shimomura M.; Tokumoto H., Meeting abstracts of the Physical Society of Japan, 62, 1, 325, 325, 28 Feb. 2007
  The Physical Society of Japan (JPS), Japanese

• 原子間力顕微鏡による発生胚皮質領域の力学測定
  岡嶋孝治
  膜、47、269-272(2022)., Aug. 2022
• 原子間力顕微鏡：多細胞系の力学物性計測の現状
  岡嶋孝治
  生物物理（解説） 62、159-164(2022), Jan. 2022
• ナノ計測 : 電子線・光・プローブ技術を用いたナノ・バイオ材料の探索と評価
  重川, 秀実; 吉村, 雅満; 目良, 裕; 岡嶋, 孝治
  近代科学社, Aug. 2020, 9784764950290, x, 179p, 図版 [4]p, Japanese
• 原子間力顕微鏡法：細胞表面近傍のナノメカニクス
  藤井裕紀; 岡嶋孝治
  表面と真空、63、437-440 (2020), 2020
• AFMによる多細胞系の力学測定
  藤井裕紀; 岡嶋孝治
  高分子、68、656-657, Dec. 2019, [Contributor]
• AFMを用いた1細胞・細胞集団の力学物性計測
  藤井裕紀; 岡嶋孝治
  生体の科学（特集：メカノバイオロジー）vol.70, No.4, Jul. 2019, [Contributor]
• 細胞ナノレオロジー：原子間力顕微鏡法
  岡嶋 孝治
  月刊ソフトマター, Sep. 2018, [Contributor]
• 走査型プローブ顕微鏡
  淺川雅; 岡嶋孝治; 大西洋
  日本分析化学会編、分析化学実技シリーズ機器分析編15, 2017, [Joint work]
• 原子間力顕微鏡による1細胞レオロジーの定量計測─細胞の個性とエルゴード性
  岡嶋 孝治
  応用物理学会誌、86、1052-1056, 2017, [Single work]
• Nanorheology of Living Cells
  T. Okajima, The World of Nano-Biomechanics (Chapter 13, A. Ikai)
  Elsevier, 2016, [Contributor]
• 原子間力顕微鏡を用いた細胞の力学特性計測
  岡嶋孝治; 高橋亮輔, 細胞の特性計測・操作と応用（組織工学ライブラリ－マイクロロボティクスとバイオの融合－ 1）（第1章・第3節）
  コロナ社, 2016, [Contributor]
• Atomic Force Microscopy: Imaging and Rheology of Living Cells
  Takaharu Okajima
  Nano/Micro Science and Technology in Biorheology: Principles, Methods, and Applications Chapter 15 (387-414), Springer, (2015), 2015, [Joint work]
• 原子間力顕微鏡を用いた細胞レオロジー特性の計測
  Okajima, Takaharu
  三次元ティッシュエンジニアリング～細胞の培養・操作・組織化から品質管理、脱細胞化まで～（第1章・第3節）、（株式会社NTS） (2015), 2015, [Joint work]
• イオンコンダクタンス顕微鏡：細胞膜表面の揺らぎを計測する
  水谷祐輔; 田中良昌; 田中あや; 住友弘二; 岡嶋孝治
  光学-細胞機能に迫る非染色非破壊イメージング技術、44, (6月号）(2015), 2015, [Joint work]
• High-throughput measurements of single cell rheology by atomic force microscopy
  K. Kuribayashi-Shigetomi; R. Takahashi; A. Subagyo; K. Sueoka; T. Okajima
  Hyper Bio Assembler for 3D Cellular Systems, Chapter 4 (57-67), Springer, 2015, 2015, [Joint work]
• 原子間力顕微鏡による超高速細胞メカニクス計測技術
  高橋亮輔; 岡嶋孝治
  ケミカルエンジニヤリング（先端計測技術開発の展望:9月号）(2015), 2015
• 細胞の物理学：ＳＰＭによる定量計測
  Okajima, Takaharu
  表面科学 35, 544-544(2014), 2014, [Joint work]
• 走査プローブ顕微鏡による細胞物性測定：原子間力顕微鏡とイオンコンダクタンス顕微鏡（総説）
  岡嶋孝治
  化学工業 (2013), 2013
• 原子間力顕微鏡による細胞力学の定量計測（解説）
  岡嶋 孝治
  検査技術 (2013), 2013
• 原子間力顕微鏡による細胞レオロジー測定（総説）
  岡嶋孝治
  日本膜学会「膜」38, 76-81 (2013), 2013
• 1細胞レオロジー測定 : 原子間力顕微鏡による細胞レオロジー計測の新手法
  岡嶋 孝治; 水谷 祐輔
  生物物理 52, 5, 230-233, Sep. 2012
• 細胞力学計測のためのマイクロ加工基板を用いた原子間力顕微鏡法
  岡嶋 孝治; 水谷 祐輔
  表面科学33(8) 461-466, Aug. 2012
• １細胞レオロジー測定：原子間力顕微鏡による細胞レオロジー計測の新手法（総説）
  岡嶋孝治; 水谷祐輔
  日本生物物理学会誌「生物物理」52, 230-233 (2012), 2012
• 走査プローブ顕微鏡（実験物理科学シリーズ6）
  共立出版, 2009
• 原子間力顕微鏡による生細胞ナノレオロジー計測
  岡嶋孝治; 徳本洋志
  日本レオロジー学会誌 vol.36, No.2, p. 81-86, Apr. 2008, [Contributor]
• ナノテクのための物理入門
  共立出版, 2007
• BioNics[バイオニクス]
  オーム社, 2005
• ソフトナノテクノロジー —バイオマテリアル革命—
  シーエムシー出版, 2005

• 発⽣組織のレオロジー普遍性の破れ
  岡嶋孝治
  AFM計測（第20回バイオオプティクス研究会, Japanese, Invited oral presentation
  13 Dec. 2024, [Invited]
• 原子間力顕微鏡による細胞レベルの発生胚メカニクス計測
  岡嶋孝治
  日本動物学会・第95回長崎大会, Japanese, Invited oral presentation
  12 Sep. 2024, [Invited]
• 発生胚メカニクスのAFM計測
  岡嶋孝治
  日本顕微鏡学会・第80回学術講演会、マルチ分解能顕微鏡、, Japanese, Invited oral presentation
  05 Jun. 2024, [Invited]
• Embryo mechanics probed by atomic force microscopy
  T. Okajima
  第61回日本生物物理学会年会, English, Invited oral presentation
  14 Nov. 2023, [Invited]
• AFMによる発⽣胚メカニクスの可視化
  岡嶋孝治
  第18回 バイオオプティクス研究会, Japanese, Invited oral presentation
  17 Dec. 2022, [Invited]
• Mapping mechanical properties of single cells during embryogenesis using atomic force microscopy
  T. Okajima
  AFM BioMED conference, (2022.8.29-9.2, Okazaki）, Dec. 2022, English, Invited oral presentation
  [Invited]
• 多細胞メカニクスの時空間マッピング測定
  岡嶋 孝治
  ナノプローブテクノロジー第167委員会 第103回研究会、高分子×SPM（2022.7.27、大岡山）, Jul. 2022, Japanese, Invited oral presentation
  [Invited]
• 原子間力顕微鏡による発生胚の力学動態の計測
  岡嶋 孝治
  第61回日本生体医工学会、細胞アッセイ：細胞動態の把握と計測、（2022.6.28-30、新潟）, Jun. 2022, Japanese, Invited oral presentation
  [Invited]
• 発生胚表面のメカニクス：原子間力顕微鏡測定
  岡嶋孝治
  日本膜学会の第44回年会、（2022.6.9-10、早稲田）, Jun. 2022, Japanese, Invited oral presentation
  [Invited]
• 細胞・組織のAFMメカニクス計測の現状と課題
  岡嶋 孝治
  バイオSPM研究会2022, Japanese
  21 Feb. 2022, [Invited]
• Nanomechanics of single cells and tissues revealed by atomic force microscopy
  T. Okajima
  Pacifichem 2021, Experimental and Computational Analysis of the Nano-Bio Interface for Sustainable Nanotechnology, (Dec.16-21, 2021, Online), Dec. 2021, English, Invited oral presentation
• Measuring mechanical properties of developing embryo with AFM
  T. Okajima
  MRS Fall meeting 2021, Frontiers in Scanning Probe Microscopy—Beyond Imaging of Soft Materials, （2021.12.6-8, Boston/Online Hybrid), Dec. 2021, English, Invited oral presentation
  [Invited]
• 発生胚のAFM計測：現状と課題
  岡嶋孝治
  第17回バイオオプティクス研究会（2021年12月10-11日、山口/オンライン）, Dec. 2021, Japanese, Invited oral presentation
  [Invited]
• AFMによる受精卵の発生過程の力学計測
  岡嶋孝治
  日本顕微鏡学会 第77回学術講演会、先端ナノプローブ法による高分解能局所物性・オペランド計測（2021年6月14日、つくば）, Jun. 2021, Japanese, Invited oral presentation
  [Invited]
• AFMによる発生胚のメカニクス
  岡嶋孝治
  2021年応物春季学術講演会, 革新的走査型プローブ顕微鏡技術で拓くナノプローブ生命科学の新展開（2021.3.16-19、onine）, Mar. 2021, Japanese, Invited oral presentation
  [Invited]
• 原子間力顕微鏡：細胞・組織のメカニクス測定
  岡嶋孝治
  日本薬剤学会・物性FGセミナー2020・顕微鏡法で医薬品原薬・製剤を“顕わ”にする―低分子から細胞まで―、2021.2.19、オンライン, Feb. 2021, Japanese, Invited oral presentation
  [Invited]
• Nanomechanics of cell and tissue probed by atomic force microscopy
  T. Okajima
  6th International Conference on Electronic Materials and Nanotechnology for Green Environment (ENGE 2020) (2020. 11.1-4, Korea_online), Nov. 2020, English, Invited oral presentation
  [Invited]
• AFMによる細胞・組織の力学情報の定量化
  岡嶋孝治
  2020年第81回応用物理学会秋季学術講演会・多次元計測技術とデータサイエンスの融合によるバイオイメージング・センシング技術の進展（京都オンライン、2020.9.9）, Sep. 2020, Japanese, Invited oral presentation
  [Invited]
• バイオAFM計測：1細胞から多細胞へ
  岡嶋孝治
  第59回日本生体医工学会大会（岡山オンライン、2020.5.25-27）, May 2020, Japanese, Invited oral presentation
  [Invited]
• 原子間力顕微鏡による細胞・組織メカニクスの定量化
  岡嶋孝治
  第67回応用物理学会春期学術講演会・多次元計測技術とデータサイエンスの融合によるバイオイメージング・センシングの将来、2020年3月12日-15日、東京, Mar. 2020, Japanese, Invited oral presentation
  [Invited]
• AFMによる1細胞・多細胞系のナノ力学計測
  岡嶋孝治
  2019年日本表面真空学会学術講演会・局所分光とバイオ計測（プローブ顕微鏡部会）（つくば、2019.10.28-30）, Oct. 2019, Japanese, Invited oral presentation
  [Invited]
• AFMによる多細胞系のメカニクス
  岡嶋孝治
  日本顕微鏡学会 ソフトマテリアル研究部会 第6回講演会（宮城蔵王、2019.10.25-26）, Oct. 2019
  [Invited]
• AFMよる1細胞・細胞集団のナノメカニクス
  岡嶋孝治
  日本顕微鏡学会第75回学術講演会・原子間力顕微鏡技術のパラダイムシフト～原子から細胞まで階層をまたぐ構造・機能解析～（名古屋、2019.6.17-19）, Jun. 2019, Japanese, Invited oral presentation
  [Invited]

• 細胞生物工学特論, 2024年, 修士課程, 情報科学院
• 細胞生物工学特論, 2024年, 博士後期課程, 情報科学研究科
• 細胞生物工学特論, 2024年, 博士後期課程, 情報科学院
• 応用数学Ⅱ, 2024年, 学士課程, 工学部
• 生体物理工学, 2024年, 学士課程, 工学部
• 生体医工学基礎, 2024年, 学士課程, 工学部
• 生体工学概論, 2024年, 学士課程, 工学部
• 生体情報工学実験Ⅰ, 2024年, 学士課程, 工学部
• 生体情報工学実験Ⅱ, 2024年, 学士課程, 工学部

• American Society for Cell Biology
• 表面科学会
• 日本生物物理学会
• 応用物理学会
• Biophysical Society（米国）

• 階層性自己組織化複合材料デザイン（代表者：松本卓也）
  CREST
  Oct. 2022 - Mar. 2028
  岡嶋孝治
  JST, 分解・劣化・安定化の精密材料科学, Coinvestigator, JPMJCR22L5
• プローブ顕微鏡による発生胚の遺伝子・力学的相互作用の解明
  科学研究費助成事業
  01 Apr. 2024 - 31 Mar. 2027
  岡嶋 孝治; 道上 達男; 繁富 香織
  日本学術振興会, 基盤研究(A), 北海道大学, 24H00412
• 原子間力顕微鏡による発生胚レオロジーの定量3D解析技術の開発
  科学研究費助成事業
  30 Jun. 2023 - 31 Mar. 2025
  岡嶋 孝治
  受精卵の胚発生は、遺伝子・生化学的因子に加えて、細胞の力学特性（メカニクス）が密接に関係していると考えられている。しかし、発生胚は極めて柔らかく、外部刺激に対して脆いため、発生胚メカニクスのタイムラプス計測に研究は少ない。最近、原子間力顕微鏡（AFM）を用いて、極めて柔らかい発生胚のメカニクスのタイムラプス計測が可能になりつつあるが、発生胚の深さ方向の力学計測技術は未開である。細胞メカニクスの主要因子である細胞骨格構造は、発生胚の表層（皮層）と内部において集積・脱離が制御されている。したがって、発生胚メカニクスの機序解明には、発生胚の深さ方向を含む３次元（3D）のレオロジー計測技術が不可欠である。本研究では、AFMの力学応答曲線のする新手法を提案し、発生胚レオロジーの定量3D計測システムの開発を目的としている。令和5年度は、3D解析を高速化するソフトウェア技術を開発した。スパースな画像を再構成することが可能な圧縮センシング法を用いて、細胞メカニクス像を再構成できることを明らかにした。また、発生胚細胞の間期において、ドット状の硬化構造が出現することを発見した。そして、この構造が、細胞分裂現象を制御している可能性があることが示唆された。さらに、 ボルツマンの重畳原理に基づく解析法と粘弾性接触理論を組み合わせた解析法を検討し、初期卵割期の各々の細胞のレオロジーを追跡することに成功した。正弦波力場の周波数（速度）と振幅（押込み量）を変動制御する新規AFM法の開発を進めた。
  日本学術振興会, 挑戦的研究(萌芽), 北海道大学, 23K17872
• Optimization of cell three-dimensional structure by computational origami and cell origami
  Grants-in-Aid for Scientific Research
  01 Apr. 2022 - 31 Mar. 2025
  繁富 香織; 上原 隆平; 堀山 貴史; 岡嶋 孝治
  近年、「折り」を基本とし、立体の形状を作る際に必要となる幾何学の問題を計算によって求める「計算折紙」と呼ばれる分野が大きな発展を遂げている。本研究では、この計算折紙の技法を細胞レベルで実装することで、2次元平面の膜状に培養した細胞を折り紙のように折り畳み、狙ったミクロな立体を効率よく形成する方法を確立する。さらに、その小立体をブロックのように組み立てて、細胞数個規模の大きさの立体から、より大きな立体を構築することを狙う。日本人が小さい頃から親しんでいる折り紙や積み木と申請者らの得意とする細胞工学や計算折紙と融合することにより、世界に先駆け、再生医療分野での全く新しいものづくりの方法を確立する。
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23K22694
• 原子間力顕微鏡による1細胞診断技術の高速化
  基盤研究(B)
  Apr. 2021 - Mar. 2024
  岡嶋 孝治
  Principal investigator
• The establishment of tissue elasticity modalities and aging control
  Grants-in-Aid for Scientific Research
  09 Jul. 2021 - 31 Mar. 2023
  早野 元詞; 岡嶋 孝治
  Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Exploratory), Keio University, 21K18608
• 原子間力顕微鏡を用いた発生胚メカニクスの包括的マッピング計測技術の開発
  挑戦的研究(萌芽)
  Apr. 2021 - Mar. 2023
  岡嶋 孝治
  Principal investigator
• In vitro pharmacological assessment of pulmonary arterial hypertension by atomic force microscopy
  Grants-in-Aid for Scientific Research
  01 Apr. 2019 - 31 Mar. 2022
  Kogaki Shigetoyo
  We established primary culture lines of pulmonary arterial smooth muscle cells (PASMCs) from a patient of idiopathic pulmonary arterial hypertension (IPAH) and a healthy control PASMC from donor lung. We analyzed their cellular mechanical properties by using atomic force microscopy. We administered the clinical available pulmonary vasodilators, then analyzed the cellular rheology of PASMCs. Sildenafil, a phosphodiesterase 5 inhibitor, could reduce cellular elasticity of PAH-PASMCs. Macitentan and riociguat could also reduce the cellular elasticity and could increase cellular fluidity of PAH-PASMCs. The combination therapy of macitentan and riociguat could effectively reduce cellular elasticity in lower concentration of the drugs, suggesting that the usefulness of combination therapy in PAH treatment.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Osaka University, 19K08276
• マルチプローブ顕微鏡技術を用いた発生胚メカニクス計測法の開発
  挑戦的研究（萌芽）
  Jul. 2019 - Mar. 2021
  岡嶋 孝治
  Principal investigator, Competitive research funding
• 細胞のエルゴード性を利用したがん細胞力学診断・アッセイ法の開発
  基盤研究(B)
  Apr. 2018 - Mar. 2021
  岡嶋 孝治
  Principal investigator, Competitive research funding
• Rheological analysis of pulmonary smooth muscle cells in pulmonary atrterial hypertension by using atomic force microscope
  Grants-in-Aid for Scientific Research
  01 Apr. 2016 - 31 Mar. 2019
  Narita Jun; KATSURAGI SHINICHI
  Recently, it was reported that the compliance of proximal pulmonary artery wall played important roles in the pathogenesis of pulmonary arterial hypertension (PAH) as well as distal pulmmonary vascular resistance did. However it was still unknown how the elasticity of pulmonary arterial smooth muscle cell (PASMC) itself can be affected in the patients of PAH. In this study, we revealed that there was a high elasticity population in PASMC of PAH patient. Additionally, Sldenafil, a drug for PAH could reduce the population of high elasticity in PASMC derived from PAH patients.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Osaka University, 16K10065
• 原子間力顕微鏡を用いた発生胚メカニクスの網羅解析法の開発
  挑戦的研究(萌芽)
  Apr. 2017 - Mar. 2019
  Okajima, Takaharu
  Principal investigator, Competitive research funding
• ヒト間葉系幹細胞治療技術の開発とその最適化に関する研究
  二国間交流事業 日本—シンガポール 共同研究
  Apr. 2015 - Mar. 2017
  Okajima, Takaharu
  Principal investigator, Competitive research funding
• 多重周波数フォースモジュレーション顕微鏡の開発：細胞レオロジー変数のイメージング
  挑戦的萌芽研究
  Apr. 2015 - Mar. 2017
  Okajima, Takaharu
  Principal investigator, Competitive research funding
• 原子間力顕微鏡による生体組織力学物性のその場分離計測技術の開発
  新学術領域研究(研究領域提案型)バイオアセンブラ
  Apr. 2014 - Mar. 2016
  Okajima, Takaharu
  バイオアセンブラにおいて、細胞システム構築に有用な細胞を分離するためには、生体組織の力学物性をダイレクトに計測する細胞分離技術が強く望まれる。原子間力顕微鏡やイオンコンダクタンス顕微鏡は、接着している細胞を低侵襲でその力学物性やダイナミクスを計測できる利点をもつ。本年度は、前年度の研究成果を基に更に高度な計測を行った。前年度に行った上皮細胞株の計測技術を基に、細胞分裂が著しく起こる発生過程の組織の直接計測を行った（論文投稿準備中）。また、マウス胎児から摘出した培養組織の力学物性と細胞骨格構造との関係を明らかにした（論文投稿準備中）。さらに、走査プローブ顕微鏡の物性マッピング速度を高速化する技術を開発し、単一細胞分離性能を向上させ、単一細胞の統計分布の精密計測に成功した（論文投稿準備中）。細胞シートの力学物性計測にも成功し、細胞シートのバルク力学物性と細胞内小器官の力学物性との関係を明らかにした（論文投稿準備中）。
  日本学術振興会, 新学術領域研究(研究領域提案型), 北海道大学, Principal investigator, Competitive research funding, 26106701
• プローブ顕微鏡による細胞間力学的相互作用の時空間揺らぎの研究
  新学術領域研究(研究領域提案型) ゆらぎと構造
  Apr. 2014 - Mar. 2016
  Okajima, Takaharu
  Principal investigator, Competitive research funding
• イオンコンダクタンス顕微鏡を用いた細胞膜揺らぎの定量イメージング技術の開発
  挑戦的萌芽研究
  Apr. 2013 - Mar. 2015
  岡嶋 孝治
  Principal investigator, Competitive research funding
• 原子間力顕微鏡を用いた細胞力学伝播関数の時空間定量解析
  基盤研究(B)
  2013 - 2015
  岡嶋 孝治
  Principal investigator, Competitive research funding
• 原子間力顕微鏡による超高速細胞レオロジー分離技術の開発
  新学術領域研究(研究領域提案型)バイオアセンブラ
  Apr. 2012 - Mar. 2014
  岡嶋孝治
  Principal investigator, Competitive research funding
• Development of cancer cell diagnostic technique using atomic force microscopy
  Grants-in-Aid for Scientific Research
  Apr. 2011 - Mar. 2013
  OKAJIMA Takaharu; SUGANUMA Masami
  Detecting cancer cells in their early stages is one of the most important techniques for diagnosing whether cells are normal or cancer. The atomic force microscopy (AFM) is a promising tool for measuring mechanical properties of cells at nano-scale. The goal of this project is to develop the cancer diagnostic tool, which is based on the measurements of cell mechanics using AFM. Micro-fabrication techniques were also employed to arrange and culture the cells on micro-patterned substrates. Two main studies in this project were (1) the development of an AFM apparatus and (2) the development of measuring and analyzing the statistical features of normal and cancer cells. We found that those micro-patterned substrates were useful for several types of normal and cancer cells. Moreover, the AFM measurements showed that the rheological properties of normal and cancer cells were largely different, i.e., the magnitude of cell modulus was lower and the number distribution of the modulus was sharper in the cancer cells. Interestingly, those exhibited a clear frequency-dependent. To control automatically the AFM system, the program based on FPGA was developed. We found that scanning ion conductance microscopy was useful for measuring the dynamic properties of cell membranes.
  Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, Principal investigator, Competitive research funding, 23656055
• 原子間力顕微鏡法を用いたがん細胞診断自動解析法の開発
  研究成果最適展開支援プログラム（A-STEP）
  2012 - 2013
  岡嶋 孝治
  Principal investigator, Competitive research funding
• Statistical Analysis of Single Cell Mechanics by Atomic Force Microscopy
  Grants-in-Aid for Scientific Research
  Apr. 2009 - Mar. 2012
  OKAJIMA Takaharu; KAWAHARA Koichi
  We investigated the number distribution of single cell rheology by atomic force microscopy (AFM) and discuss the statistical data in connection with a modern model of cell rheology such as power-law rheology. (1) The number distribution of single cell rheology was measured as a function of external frequency. (2) The rheological behavior of cells was measured as cells were synchronized using serum starvation. (3) We succeeded to measure the ensemble-and time-averaged cell rheology and found differences between them. (4) We investigated the number distribution of power-law rheology of cells transformed from normal cells to immortalized cells.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Principal investigator, Competitive research funding, 21310079
• 細胞周期制御下の細胞界面ナノダイナミクスの研究
  科学研究費助成事業
  Apr. 2009 - Mar. 2011
  岡嶋 孝治
  原子間力顕微鏡法(AHM)や種々の蛍光計測法を用いて、細胞周期(G1期、S期、G2期、M期)を制御した細胞界面ナノ領域の力学・ダイナミクス測定を行い、細胞周期に対する細胞界面ナノ物性を明らかにすることを目的として研究を行った。細胞周期を同定できる蛍光タンパク質を発現した細胞を用いて、細胞周期と細胞レオロジーとの関係を調べた。原子間力顕微鏡(AFM)計測により、全ての細胞周期において、複素弾性率の周波数特性はべき関数を示し、弾性振幅は、G1期やS/G2期に比べて、S期初期で増大することが分かった。また、G1期細胞のべき指数は、それ以外の細胞周期に比べて増大し、G1期の細胞は、他の細胞期に比べて流動的になることが分かった。細胞レオロジーが細胞周期に強く依存することが明らかになってきたが、細胞界面から内部への力学伝播に関する知見は皆無であり、その計測方法も欠如している。そこで、細胞内の力伝播を直接測定する方法を開発した。本方法は、力センサであるマイクロポスト基板上に培養した細胞の上部からAFMで力学刺激を与えて、細胞上部から細胞下部への力伝播をマイクロポストセンサーにより計測する方法である。周波数測定において細胞力伝播が弾性的であることが分かった。エンドサイトーシスを効率的に誘導する分子として、N-アセチルグルコサミン(GlcNAc)を有する高分子鎖が腫瘍細胞(HT1080)のエンドサイトーシスを強く誘導することを見つけた。
  特定領域研究・高次系分子科学, 特定領域研究, 北海道大学, Principal investigator, Competitive research funding, 22018003
• 走査プローブ顕微鏡と蛍光相関分光法による生細胞界面の1分子ダイナミクスの研究
  科学研究費助成事業
  Apr. 2008 - Mar. 2010
  岡嶋 孝治
  細胞界面ダイナミクスや力学特性には、時空間不均一性や細胞の個性が存在するが、そのような細胞状態を制御した計測はこれまでなされていない。例えば、細胞周期により細胞はその状態を大きく変化させていると考えられるが、細胞周期に対する細胞界面ナノ物性は不明である。そこで、本研究では、AFMを用いて、細胞周期を同調させた細胞を作成し、細胞周期と細胞界面ダイナミクスを調べた。細胞周期を同調させるために、血清飢餓法を用いた。本手法は、低侵襲で細胞をG1期に同調させることができる。AFMとマイクロアレイ技術を用いて、細胞界面ダイナミクス(複素弾性率)を測定した。その結果、細胞周期を同調した細胞の複素弾性率の細胞数分布は、非同調細胞と同様に対数分布を有することが分かった。また、複素弾性率の周波数依存性は、べき関数応答を示すことが分かった。そこで、細胞の複素弾性率を表現するモデルとして、構造ダンピングモデルを用いて、細胞周期同調細胞および非同調細胞とのべき指数および粘性応答を解析した。その結果、両者のべき指数の平均値と分散は等しく細胞骨格構造の力学特性は細胞周期に強く依存しないことが分かった。一方で、細胞粘性応答は、両者で大きく異なることが分かった。このことは、細胞周期を同調させる過程において、細胞内タンパク質状態が変化したことを示唆した。また、細胞膜脂質分子の細胞界面ダイナミクス測定を行った。その結果、細胞膜脂質分子の細胞内取り込み量は、M期に比べてG1/S期で増大し、その取り込み量が、細胞膜のコレステロールと強く関係していることが分かった。
  特定領域研究・高次系分子科学, 特定領域研究, 北海道大学, Principal investigator, Competitive research funding, 20050001
• 単一細胞表層の全方向ナノダイナミクス計測技術の開発
  産業技術研究助成事業
  2006 - 2009
  岡嶋孝治
  NEDO, 産業技術研究助成事業, Principal investigator
• 糖鎖1分子のナノ力学刺激に対する応答ダイナミクスの研究
  科学研究費助成事業
  Apr. 2005 - Mar. 2007
  岡嶋 孝治
  多糖類は、特異の立体規則性をもち、選択的な相互作用をする。この固有な性質により、細胞膜での認識機構や、細胞外マトリクスの主要物質であるなど、多糖類は、生体の階層構造の形成において、極めて重要な役割を果たしている。このような巨大高分子の非保存力を測定する手法は、まだ十分に確立していない。本研究では、原子間力顕微鏡(AFM)による新規な単一分子の操作技術として、高分子ゲル中に埋め込まれた分子鎖をゲル外に引く抜くときの力学的性質を調べる手法を開発した。その結果、分子鎖が一定張力や非線形聴力引き抜かれること、そして、網目構造と1分子力学特性との関係を初めて測定することができた。(論文印刷中)。本計測法は、準希薄媒体や濃厚媒体の中で1分子計測を可能とする新手法であり、巨大高分子鎖間の相互作用を1分子レベルで探索することを可能とする。次に、細胞膜付近のダイナミクスを測定するための方法として、ATFによる応力緩和計測法を開発した。そして、サブマイクロメートル領域の応力緩和挙動のダイナミクスと局所弾性率との関係を初めて明らかにした(論文印刷中)。さらに、ナノ力学刺激の応答の定量計測を目指して、1μm以下のコロイドビーズをプローブした、高分解能コロイドプローブ顕微鏡技術を構築し、その性能評価を行った。その結果、サンプルの深さ方向および水平方向の分解能が、共に向上することが分かった(論文投稿準備中)。本結果は、細胞外マトリクスのようなゲル様の多糖高分子ナノ構造を探索するための強力な手法になると期待できる。
  萌芽研究, 萌芽研究, 北海道大学, Principal investigator, Competitive research funding, 17655097
• Research of Carbon-Nanotube-AFM for Exploring Inside Biological Cells
  Grants-in-Aid for Scientific Research
  2004 - 2006
  TOKUMOTO Hiroshi; OKAJIMA Takaharu; AZEHARA Hiroaki
  AFM is the very powerful tool for surface science and is now extending its application to the biotechnology field where a single molecule and protein will be observed in an appropriate condition. And now in this project, we will try to develop a technique to explore the internal structures or functions of the cell. Here, we will develop key techniques for bio-AFM using carbon nanotube(CNT) as its tip: First we have prepared stable CNT-AFM tips fixed onto commercial Si-AFM tips. At the same time, we fabricated the artificial lipid bilayer membranes using dimyristoyl phosphatidyl choline (DMPC) molecules. And then we penetrated the former CNT-AFM tip through the DMPC bilayer film while measuring the forces between the tip and the membrane. Further, we successfully modified chemically an end of the CNT tip, where -COOH's were fixed, by simply cutting CNT in a low vacuum environment of SEM. As a test sample, we prepared patterned structure on Au substrate consisting of hydrophobic and hydrophilic parts with the aid of the micro-contact printing technique. By measuring the weak forces between chemically modified CNT-tip and the test sample, we have discriminated the two parts very clearly, indicating that we have successfully demonstrated the ability of the chemical force AFM. Under this success in mind, we will be able to recognize the individual bases in a DNA molecule using this technique. Inside and outside of cells, there is various bio-molecules which may interact nonspecifically with AFM tips. We measured these forces using PEG polymer incorporated into polymer gels and found specific forces as expected. At the same time, we have developed the good technique to manipulate a single polymer. By measuring the stress relaxation of HepG2 cells using AFM, we have obtained information on dynamic elasticity of the living cells. From these results, we will open a new mechanical technique for obtaining the information to understand the relationship between structure and function of living cells.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 16310078
• 生体分子のマイクロ秒粘弾性測定
  科学研究費助成事業
  Apr. 2003 - Mar. 2005
  岡嶋 孝治
  本研究では、原子間力顕微鏡(AFM)の高い時間空間分解能を最大限に活用し、生体一分子に働く張力の粘弾性挙動を計測する基礎技術の開発が目的である。1分子の外部環境依存性、および広帯域計測に不可欠な長時間計測を実現するためには、装置ドリフトの影響を抑える手法の開発が必要不可欠である。ミリ秒の帯域の1分子計測においても、AFM装置に不可避に存在するドリフトが計測精度に与える影響が大きいことが分かった。そこで、AFM探針と基板との間のドリフトを補償する技術の開発を行った。本方法は、自作の延伸軸補正用コントローラを用いて、分子と探針との間の相対位置情報を取得し、分子が基板と接触している点(剥がし点)と探針の位置とを結ぶ直線が基板面に対して常に垂直になるように制御する。これにより、装置のドリフトを補正した長時間延伸が可能となった。
  一方で、生体分子の粘弾性には、分子内の相互作用に起因するものと分子外の相互作用によるものに分けられるが、特に分子外の相互作用を1分子レベルで計測する手法は確立されていない。そこで、分子外の非特異的相互作用を計測する手法を考案した。本方法は、高分子ゲルにターゲットなる高分子鎖を埋め込み、その埋め込んだ高分子をゲルから引っ張り出すときに生じる力から、分子外相互作用を測定する。本方法を用いて、摩擦力やトポロジカルな相互作用を1分子レベルで計測することが可能となった。さらに、生体分子の粘弾性を固体基板上ではなく、細胞表面で測定することを念頭として、細胞表面を精密に計測する手法を考案し、その有効性を確証した。これらの技術を特許出願することにより、1分子粘弾性計測法の基幹技術を構築した。
  若手研究(B), 若手研究(B), 北海道大学, Principal investigator, Competitive research funding, 15710084
• 原子間力顕微鏡を用いた単一高分子鎖の相転移における力学緩和の測定
  若手研究(B)
  Apr. 1999 - Mar. 2001
  岡嶋 孝治
  本研究では、原子間力顕微鏡が本質的にもっている高空間・時間分解能を利用して、単一高分子鎖のダイナミクスを計測する方法を確立し、合成高分子やタンパク質の構造転移における動的挙動を調べることを目的としている。
  前年度に引き続き、球状タンパク質として、力-延伸特性が良く分かっているウシ由来炭酸デヒドラターゼの変異体を用いて、アンフォールディング近傍にタンパク質一分子の交流変位応答を測定した。その結果、活性をもつ天然型のタンパク質では、部分的な構造のアンフォールドとリフォールドに対応する力学応答が観測され、一方で、活性をもたず構造が緩い分子では、ゴム弾性に相当する単調な応答のみが観測されることが分かつた。本研究結果は、Biochem. Phys.に現在投稿中である。
  原子間力顕微鏡(AFM)の一分子測定を発展させる過程で、これまで液中では不可能と思われてきた自励発振技術を、液中でも安定に動作させられることを見つけた。この新しい周波数変調(FM)法に基づく液中用AFM装置の接触力は数10pNであり、世界最高レベルの液中イメージングが可能であることが分かった。特に、FM法は走査速度の制限を受けない点で従来の液中測定装置よりも優れており、今後、本方法が液中観察の標準的な方法になると期待される。自励発振型のAFM装置を用いて、雲母基板に固定処理を全く施していない繊維状タンパク質(タウタンパク質)の液中イメージングを行った。その結果、生体分子をほとんど変形させないほど弱い接触力でイメージングが可能であることが分かり、また、また度重なるイメージングにおいてもタンパク質分子が破壊されないことが分かった。この結果から、生理条件下における任意の生体分子の"真"の構造を高分解能で観察できる可能性が示唆された。
  日本学術振興会, 若手研究(B), 東京工業大学, Principal investigator, Competitive research funding, 13740251
• シェアフォース顕微鏡におけるプローブ・表面間相互作用の起源の解明
  奨励研究(A)
  Apr. 1997 - Mar. 1999
  岡嶋 孝治
  平成9年度は、光検出型シェアフォース顕微鏡を用いて、シェアフォース相互作用の湿度依存性とプローブのバネ定数依存性を研究した。その結果、低湿度におけるシェアフォース相互作用は、プローブと表面の間の接触相互作用に起因し、高湿度のそれは、毛管凝集力に密接に関連する事がわかった。平成10年度は、まず、1997年にRuiter等とAtia等により開発された、音叉検出型シェアフォース顕微鏡を、新たに試作した。本装置は、プローブの共振周波数変化と振幅変化;こ追従できる回路を用いる事により、シェアフォース相互作用を高精度で測定する事ができる。本装置を用いて、前年度の研究の再検討を行った結果は、光検出型シェアフォース顕微鏡で得られた結果と同様であり、測定法の違いによる顕著な違いはなかった。以上の結果は、以前にGregor等により提案されたプローブ・表面の接触モデルと多くの不一致が生じる事がわかった。研究代表者は、本結果を説明するために、プローブの振動不安定性がシェアフォース相互作用と密接に関係している事を提案した。
  高湿度におけるプロープと表面間の接触時間とシェアフォース相互作用の関係を調べた結果、毛管凝集力に起因する相互作用のヒステリシス距離は、ほとんど変化しない事がわかった。この結果は、プローブと表面が接触すると、吸着水が1sec程度で、急速に凝集する事を示唆する。
  シェアフォース顕微鏡における、表面及び表面近傍の粘性、弾性の物性測定の可能性を評価するための試料の探索の中で、高分子ゲルの網目構造とその体積緩和の間に関する新たな現象を見つけた。
  日本学術振興会, 奨励研究(A), 東京工業大学, Principal investigator, Competitive research funding, 09750074
• Research on Basic Properties and Structure of ionized Gels
  Grants-in-Aid for Scientific Research
  1998 - 1999
  HIROTSU Shunsuke; OKAJIMA Takaharu
  Reasearch on the mechanism of the volume phase transition : Traditional view on the mechanism of the volume phase transition in gels has been critically analyzed. We have proposed a new model of the volume phase transition in which the shrunken phase is not a get but a precipitated network. Experimental evidences supporting this new model have been obtained by dynamic light scattering and elastic relaxation measurements.
  Meso-phase formation in ionized gels : Formation of mesoscopic structure accompanied by charge separation has been investigated by static and dynamic light scattering. A clear evidence of meso-phase formation have been obtained both in relaxation and intensity of the scattered light. This is the first example demonstrating that the meso-phase can be studied not only by neutron but also visible light.
  Elastic measurements near the volume phase transition : A new apparatus for mesuring elastic constants and elastic relaxation has been built. Using this apparatus elastic behaviors around the volume phase transition have been succesfully measured.
  Structural differences between biologal polymer gels and synthesized gels : In terms of light scattering measurements, the structural difference between acrylamide family gels and bilogical polysaccharides has been studied. The difference is considered to be due mainly to the difference in crosslinking mechanisms.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), TOKYO INSTITUTE OF TECHNOLOGY, 10440116
• 温度敏感性ゲルを用いた細胞培養による細胞の応力応答の研究
  科学研究費助成事業
  1997 - 1998
  弘津 俊輔; 岡嶋 孝治
  本年度に行った研究とその成果を以下にまとめた。
  1) 温度敏感性ゲルの相転移を利用した、細胞への応力印加の実験。: これについては、ゼラチンを混入したNIPAゲルを用いて、試行実験を行った。結果は、膨潤相から収縮相への変化に関しては目立った効果は見られなかった。現在、細胞に有効に力を印可する方法を開発すると共に、収縮相から膨潤相への転移の効果も調べつつある。
  2) 化学架橋ゼラチンゲル基盤の合成: 細胞接着性が良好で、しかも比較的自由に弾性的性質を調節出来る基盤として、ゼラチンとコハク化ゼラチンの混合物をカルボジイミドで架橋したゲルを開発した。ゼラチンとコハク化ゼラチンの混合比を変えることにより、弾性率が同じで、膨潤率が異なるゲルを得ることが出来た。
  3) ゲルの弾性率測定: 電子天秤を利用してゲルに一定の加重を印可し、その変形から、ゲルの静的弾性率(ヤング率、合成率、および体積弾性率)を決定した。
  4) ゲル基盤の弾性的性質と培養細胞の形状との関係
  基盤(足場)と細胞との力学的相互作用が、細胞の機能、増殖能、形状などに与える影響を理解するためには、基盤の弾性的性質が細胞に与える効果を調べる必要がある。上記の方針で、弾性率を測定したゲルで、マウス3T3繊維芽細胞を培養してその形状を調べた結果、細胞形状は基盤の堅さに強く依存することが分かった。具体的には、基盤ゲルのヤング率が1x10^4[dyn/cm^2]以上の場合、7x10^3〜1x10^4[dyn/cm^2]、7x10^3[dyn/cm^2]以下の場合のそれぞれに応じて、細胞の外径および増殖のパターンに顕著な相違が見られた。より詳しい解析を実行中である。
  日本学術振興会, 萌芽的研究, 東京工業大学, 09875243

• 力学物性の測定方法、プローブの押し込み量の制御方法および力学物性の測定装置
  Patent right, 岡嶋 孝治、小谷 崇博、内橋 貴之、チャン・フォンユエ, Hokkaido University
  特願2025-091112, 30 May 2025
• 特願2024-90859、力学物性の測定方法、プローブの押し込み量の制御方法および力学物性の測定装置、北海道大学・名古屋大学（2024年6月4日）
  Patent right, 岡嶋 孝治; 小谷 崇博; 内橋 貴之; チャン・フォンユエ, Hokkaido University
  特願特願2024-90859、, 04 Jun. 2024
• 原子間力顕微鏡による単一細胞の力学的診断方法と診断装置
  Patent right, 岡嶋孝治; 高橋亮輔
  特願2017-55414, 22 Mar. 2017
• 酵母細胞の力学特性の測定方法、及び力学特性に基づいた酵母細胞のスクリーニング方法
  Patent right, 有友亮太; 潮井徹; 岡嶋孝治; 田中良昌
  特願特願2016-176540, 09 Sep. 2016
• 細胞足場材料、細胞モデル、及び細胞足場材料の製造方法
  Patent right, 田中あや; 手島哲彦; 中島寛; 岡嶋孝治; 藤井裕紀
  特願2017-032733, 23 Feb. 2016
• 細胞の複素弾性率の計測方法および計測システム
  Patent right, 岡嶋孝治; 高橋亮輔
  特願2014-136721, 02 Jul. 2014
• 単一細胞の力学特性の計測方法および計測装置
  Patent right, 岡嶋孝治; 蔡萍根; 水谷祐輔; 土屋雅博
  特願2011-184403, 26 Aug. 2011
  特願2011-184403
• 原子間力顕微鏡用のコロイドプローブカンチレバーの製造方法および製造装置
  Patent right
  特願2007-287126
• Surface Position Measuring Method and Surface Position Measuring Device
  Patent right
  WO 2006/073068
• Device and Method for Measuring Molecule Using Gel Substrate Material
  Patent right
  WO 2006/028135
• Molecular Measuring Device and Molecule Measuring Method
  Patent right
  WO 2006/011348