Katsuhiko Sato |

Research Institute for Electronic Science |

Associate Professor |

Last Updated :2023/09/05

- Master's degree program Graduate School of Life Science
- Doctoral (PhD) degree program Graduate School of Life Science

- Syun Echigoya, Katsuhiko Sato, Osamu Kishida, Toshiyuki Nakagaki, Yukinori NishigamiFrontiers in Cell and Developmental Biology 10 1021469 2022/11/01 [Refereed][Not invited]
- Satoru Okuda, Katsuhiko Sato, Tetsuya HiraiwaThe European Physical Journal E 45 (8) 1292-8941 2022/08
- Katsuhiko Sato, Daiki UmetsuFrontiers in Physics 9 2021/07/22 [Refereed][Invited]

The vertex model is a useful mathematical model to describe the dynamics of epithelial cell sheets. However, existing vertex models do not distinguish contraction forces on the cell boundary from adhesion between cells, employing a single parameter to express both. In this paper, we introduce the rest length of the cell boundary and its dynamics into the existing vertex model, giving a novel formulation of the model that treats separately the contraction force and the strength of adhesion between cells. We apply this vertex model to the phenomenon of compartment boundary in the fruit fly pupa, recapturing the observation that increasing the strength of adhesion between cells straightens the compartment boundary, even though contraction forces at cell boundaries remain unchanged. We also discuss possibilities of the novel vertex models by considering the stretching of a cell sheet by external forces. - Norihiro Iijima, Katsuhiko Sato, Erina Kuranaga, Daiki UmetsuNature Communications 11 (1) 6320 - 6320 2020/12 [Refereed]

Abstract Maintaining lineage restriction boundaries in proliferating tissues is vital to animal development. A long-standing thermodynamics theory, the differential adhesion hypothesis, attributes cell sorting phenomena to differentially expressed adhesion molecules. However, the contribution of the differential adhesion system during tissue morphogenesis has been unsubstantiated despite substantial theoretical support. Here, we report that Toll-1, a transmembrane receptor protein, acts as a differentially expressed adhesion molecule that straightens the fluctuating anteroposterior compartment boundary in the abdominal epidermal epithelium of theDrosophila pupa.Toll-1 is expressed across the entire posterior compartment under the control of the selector geneengrailed and displays a sharp expression boundary that coincides with the compartment boundary.Toll-1 corrects local distortions of the boundary in the absence of cable-like Myosin II enrichment along the boundary. The reinforced adhesion of homotypic cell contacts, together with pulsed cell contraction, achieves a biased vertex sliding action by resisting the separation of homotypic cell contacts in boundary cells. This work reveals a self-organizing system that integrates a differential adhesion system with pulsed contraction of cells to maintain lineage restriction boundaries. - Schenz D, Nishigami Y, Sato K, Nakagaki TCurrent opinion in genetics & development 57 78 - 83 0959-437X 2019/08 [Refereed][Not invited]
- Okuda S, Kuranaga E, Sato KBiophysical journal 116 (6) 1159 - 1170 0006-3495 2019/03 [Refereed][Not invited]

Epithelial sheet integrity is robustly maintained during morphogenesis, which is essential to shape organs and embryos. While maintaining the planar monolayer in three-dimensional space, cells dynamically flow via rearranging their connections between each other. However, little is known about how cells maintain the plane sheet integrity in three-dimensional space and provide cell flow in the in-plane sheet. In this study, using a three-dimensional vertex model, we demonstrate that apical junctional fluctuations allow stable cell rearrangements while ensuring monolayer integrity. In addition to the fluctuations, direction-dependent contraction on the apical cell boundaries, which corresponds to forces from adherens junctions, induces cell flow in a definite direction. We compared the kinematic behaviors of this apical-force-driven cell flow with those of typical cell flow that is driven by forces generated on basal regions and revealed the characteristic differences between them. These differences can be used to distinguish the mechanism of epithelial cell flow observed in experiments, i.e., whether it is apical- or basal-force-driven. Our numerical simulations suggest that cells actively generate fluctuations and use them to regulate both epithelial integrity and plasticity during morphogenesis. - Hiroshi Orihara, Katsuhiko SatoNihon Reoroji Gakkaishi 38 (4) 262 - 269 0387-1533 2019 [Invited]
- Yoshinori Takikawa, Muneharu Yasuta, Shuji Fujii, Hiroshi Orihara, Yoshimi Tanaka, Katsuyoshi NishinariJournal of the Physical Society of Japan 87 (5) 054005/1 - 054005/4 1347-4073 2018 [Refereed][Not invited]

Xanthan gum exhibits viscoelastic and shear-thinning properties. We investigate the Brownian motion of particles dispersed in xanthan gum solutions that are subjected to simple shear flow. The mean square displacements (MSDs) are obtained in both the flow and vorticity directions. In the absence of shear flow, subdiffusion is observed, MSD ∝ tα with α > 1, where t is time. In the presence of shear flow, however, the exponent α becomes larger together with the MSD itself in both the flow and vorticity directions. We show that the diffusion is enhanced by Taylor dispersion in the flow direction, whereas in the vorticity direction it is enhanced by nonthermal self-diffusion. **モジホコリ**高木 清二, 佐藤 勝彦, 中垣 俊之生物工学 96 (8) 488 - 492 2018 [Not refereed][Invited]- Katsuhiko SatoDEVELOPMENT GROWTH & DIFFERENTIATION 59 (5) 317 - 328 0012-1592 2017/06 [Refereed][Not invited]

During early embryonic development, epithelial cells form a monolayer sheet and migrate in a definite direction. This phenomenon, called epithelial cell migration, is an important topic in developmental biology. A characteristic feature of this process is attachment to adjacent cells during migration, which is necessary for maintaining the integrity of the sheet. However, it is unclear how these cohesive cells migrate without breaking their attachments. A mechanism for this phenomenon was recently proposed, in which direction-dependent contraction forces acting on cell boundaries induce unidirectional epithelial migration. In this review, we examine this proposed mechanism from various aspects and provide theoretical background for the collective migration of epithelial cells. This information may be helpful for investigators to realize the basic principles underlying collective epithelial migration and devise new mechanisms for it. - Dai Akita, Daniel Schenz, Shigeru Kuroda, Katsuhiko Sato, Kei-ichi Ueda, Toshiyuki NakagakiDEVELOPMENT GROWTH & DIFFERENTIATION 59 (5) 465 - 470 0012-1592 2017/06 [Refereed][Not invited]

Vein networks span the whole body of the amoeboid organism in the plasmodial slime mould Physarum polycephalum, and the network topology is rearranged within an hour in response to spatio-temporal variations of the environment. It has been reported that this tube morphogenesis is capable of solving mazes, and a mathematical model, named the current reinforcement rule', was proposed based on the adaptability of the veins. Although it is known that this model works well for reproducing some key characters of the organism's maze-solving behaviour, one important issue is still open: In the real organism, the thick veins tend to trace the shortest possible route by cutting the corners at the turn of corridors, following a center-in-center trajectory, but it has not yet been examined whether this feature also appears in the mathematical model, using corridors of finite width. In this report, we confirm that the mathematical model reproduces the center-in-center trajectory of veins around corners observed in the maze-solving experiment. - K. Sato, I. Kunita, Y. Takikawa, D. Takeuchi, Y. Tanaka, T. Nakagaki, H. OriharaSOFT MATTER 13 (14) 2708 - 2716 1744-683X 2017/04 [Refereed][Not invited]

Shear banding is frequently observed in complex fluids. However, the configuration of macromolecules in solutions undergoing shear banding has not yet been directly observed. In this study, by using the fact that F-actin solutions exhibit shear banding and actin filaments are visualized by fluorescent labels, we directly observed the intrinsic states of an actin solution undergoing shear banding. By combining the 3D imaging of labeled actin filaments and particle image velocimetry (PIV), we obtained orientation distributions of actin filaments in both high and low shear rate regions, whose quantitative differences are indicated. In addition, by using the orientation distributions and applying stress expression for rod-like polymers, we estimated stress tensors in both high and low shear rate regions. This evaluation indicates that different orientation distributions of filamentous macromolecules can exhibit a common shear stress. - Shin'ichi Ishiwata, Makito Miyazaki, Katsuhiko Sato, Koutaro Nakagome, Seine A. Shintani, Fuyu Kobirumaki-Shimozawa, Norio Fukuda, Kazuya Suzuki, Jun Takagi, Yuta Shimamoto, Takeshi ItabashiMOLECULAR CRYSTALS AND LIQUID CRYSTALS 647 (1) 127 - 150 1542-1406 2017 [Refereed][Invited]

Bio-motile systems have liquid-crystalline structures. This review first describes the contractile system of striated muscle having a smectic liquid crystalline structure. We here report the muscle's auto-oscillatory property named spontaneous oscillatory contraction (SPOC) [1], and a mathematical model to explain its mechanism [2, 3]. Also, sarcomere dynamics observed during heartbeat are described. The second topic is the micromechanics of the meiotic spindle, a bipolar assembly of microtubules with chromosomes [4]. The third topic is the demonstration of a contractile actin ring spontaneously formed inside a water-in-oil droplet, which can be considered as an artificial cell model [5]. - Dai Akita, Itsuki Kunita, Mark D. Fricker, Shigeru Kuroda, Katsuhiko Sato, Toshiyuki NakagakiJOURNAL OF PHYSICS D-APPLIED PHYSICS 50 (2) 024001 0022-3727 2017/01 [Refereed][Not invited]

Transport networks are ubiquitous in multicellular organisms and include leaf veins, fungal mycelia and blood vessels. While transport of materials and signals through the network plays a crucial role in maintaining the living system, the transport capacity of the network can best be understood in terms of hydrodynamics. We report here that plasmodium from the large, single-celled amoeboid Physarum was able to construct a hydrodynamically optimized veinnetwork when evacuating biomass from confined arenas of various shapes through a narrow exit. Increasingly thick veins developed towards the exit, and the network spanned the arena via repetitive bifurcations to give a branching tree. The Hausdorff distance from all parts of the plasmodium to the vein network was kept low, whilst the hydrodynamic conductivity from distal parts of the network to the exit was equivalent, irrespective of the arena shape. This combination of spatial patterning and differential vein thickening served to evacuate biomass at an equivalent rate across the entire arena. The scaling relationship at the vein branches was determined experimentally to be 2.53-3.29, consistent with predictions from Murray's law. Furthermore, we show that mathematical models for self-organised, adaptive transport in Physarum simulate the experimental network organisation well if the scaling coefficient of the current-reinforcement rule is set to 3. In simulations, this resulted in rapid development of an optimal network that minimised the combined volume and frictional energy in comparison with other scaling coefficients. This would predict that the boundary shear forces within each vein are constant throughout the network, and would be consistent with a feedback mechanism based on a sensing a threshold shear at the vein wall. - Nakagome K, Sato K, Shintani SA, Ishiwata SBiophysics and physicobiology 13 217 - 226 2189-4779 2016 [Refereed][Not invited]

SPOC (spontaneous oscillatory contraction) is a phenomenon observed in striated muscle under intermediate activation conditions. Recently, we constructed a theoretical model of SPOC for a sarcomere, a unit sarcomere model, which explains the behavior of SPOC at each sarcomere level. We also constructed a single myofibril model, which visco-elastically connects the unit model in series, and explains the behaviors of SPOC at the myofibril level. In the present study, to understand the SPOC properties in a bundle of myofibrils, we extended the single myofibril model to a two-dimensional (2D) model and a three-dimensional (3D) model, in which myofibrils were elastically connected side-by-side through cross-linkers between the Z-lines and M-lines. These 2D and 3D myofibril models could reproduce various patterns of SPOC waves experimentally observed in a 2D sheet and a 3D bundle of myofibrils only by choosing different values of elastic constants of the cross-linkers and the external spring. The results of these 2D and 3D myofibril models provide insight into the SPOC properties of the higher-ordered assembly of myofibrils. - Katsuhiko Sato, Tetsuya Hiraiwa, Emi Maekawa, Ayako Isomura, Tatsuo Shibata, Erina KuranagaNATURE COMMUNICATIONS 6 10074 2041-1723 2015/12 [Refereed][Not invited]

Morphogenetic epithelial movement occurs during embryogenesis and drives complex tissue formation. However, how epithelial cells coordinate their unidirectional movement while maintaining epithelial integrity is unclear. Here we propose a novel mechanism for collective epithelial cell movement based on Drosophila genitalia rotation, in which epithelial tissue rotates clockwise around the genitalia. We found that this cell movement occurs autonomously and requires myosin II. The moving cells exhibit repeated left-right-biased junction remodelling, while maintaining adhesion with their neighbours, in association with a polarized myosin II distribution. Reducing myosinID, known to cause counter-clockwise epithelial-tissue movement, reverses the myosin II distribution. Numerical simulations revealed that a left-right asymmetry in cell intercalation is sufficient to induce unidirectional cellular movement. The cellular movement direction is also associated with planar cell-shape chirality. These findings support a model in which left-right asymmetric cell intercalation within an epithelial sheet drives collective cellular movement in the same direction. - Katsuhiko Sato, Shin-ichiro ShimaPHYSICAL REVIEW E 92 (4) 042922 1539-3755 2015/10 [Refereed][Not invited]

We investigate a phase model that includes both locally attractive and globally repulsive coupling in one dimension. This model exhibits nontrivial spatiotemporal patterns that have not been observed in systems that contain only local or global coupling. Depending on the relative strengths of the local and global coupling and on the form of global coupling, the system can show a spatially uniform state (in-phase synchronization), a monotonically increasing state (traveling wave), and three types of oscillations of relative phase difference. One of the oscillations of relative phase difference has the characteristic of being locally unstable but globally attractive. That is, any small perturbation to the periodic orbit in phase space destroys its periodic motion, but after a long time the system returns to the original periodic orbit. This behavior is closely related to the emergence of saddle two-cluster states for global coupling only, which are connected to each other by attractive heteroclinic orbits. The mechanism of occurrence of this type of oscillation is discussed. - Katsuhiko Sato, Tetsuya Hiraiwa, Tatsuo ShibataPHYSICAL REVIEW LETTERS 115 (18) 188102 0031-9007 2015/10 [Refereed][Not invited]

During early development, epithelial cells form a monolayer sheet and migrate in a uniform direction. Here, we address how this collective migration can occur without breaking the cell-to-cell attachments. Repeated contraction and expansion of the cell-to-cell interfaces enables the cells to rearrange their positions autonomously within the sheet. We show that when the interface tension is strengthened in a direction that is tilted from the body axis, cell rearrangements occur in such a way that unidirectional movement is induced. We use a vertex model to demonstrate that such anisotropic tension can generate the unidirectional motion of cell sheets. Our results suggest that cell chirality facilitates collective cell migration during tissue morphogenesis. - Yuji Sasaki, Yoshinori Takikawa, V. S. R. Jampani, Hikaru Hoshikawa, Takafumi Seto, Christian Bahr, Stephan Herminghaus, Yoshiki Hidaka, Hiroshi OriharaSOFT MATTER 10 (44) 8813 - 8820 1744-683X 2014 [Refereed][Not invited]

Tunable transport of tiny objects in fluid systems is demanding in diverse fields of science such as drug delivery, active matter far from equilibrium, and lab-on-a-chip applications. Here, we report the directed motion of colloidal particles and self-assembled colloidal chains in a nematic liquid crystal matrix using electrohydrodynamic convection (EHC) rolls. The asymmetric distortion of the molecular orientation around the particles results - for single particles - in a hopping motion from one EHC roll to the next and - for colloidal chains - in a caterpillar-like motion in the direction perpendicular to the roll axes. We demonstrate the use of colloidal chains as microtraction engines for the transport of various types of microcargo. - Itsuki Kunita, Katsuhiko Sato, Yoshimi Tanaka, Yoshinori Takikawa, Hiroshi Orihara, Toshiyuki NakagakiSeibutsu Butsuri 一般社団法人 日本生物物理学会 54 (1) S280 2014
- Yoshinori Takikawa, Hiroshi OriharaPHYSICAL REVIEW E 88 (6) 062111.1 - 062111.5 1539-3755 2013/12 [Refereed][Not invited]

The persistence of a Brownian particle in a shear flow is investigated. The persistence probability P(t), which is the probability that the particle does not return to its initial position up to time t, is known to obey a power law P(t) proportional to t(-theta) Since the displacement of a particle along the flow direction due to convection is much larger than that due to Brownian motion, we define an alternative displacement in which the convection effect is removed. We derive theoretically the two-time correlation function and the persistence exponent. of this displacement. The exponent has different values at short and long times. The theoretical results are compared with experiment and a good agreement is found. - Katsuhiko Sato, Yoshiki Kuramoto, Masako Ohtaki, Yuta Shimamoto, Shin'ichi IshiwataPHYSICAL REVIEW LETTERS 111 (10) 108104 0031-9007 2013/09 [Refereed][Not invited]

At an intermediate activation level, striated muscle exhibits autonomous oscillations called SPOC, in which the basic contractile units, sarcomeres, oscillate in length, and various oscillatory patterns such as traveling waves and their disrupted forms appear in a myofibril. Here we show that these patterns are reproduced by mechanically connecting in series the unit model that explains characteristics of SPOC at the single-sarcomere level. We further reduce the connected model to phase equations, revealing that the combination of local and global couplings is crucial to the emergence of these patterns. - Yoshinori Takikawa, Hiroshi OriharaJOURNAL OF THE PHYSICAL SOCIETY OF JAPAN 81 (12) 124001.1-124001.5 0031-9015 2012/12 [Not refereed][Not invited]

Brownian motion has been investigated in oscillatory flows. A number of polystyrene spheres dispersed in water were traced with a confocal scanning laser microscope, and the time dependences of their coordinates were obtained. From the trajectories of the particles observed, mean-square displacements (MSDs) were calculated. We found that although the MSD in the vorticity direction is independent of the amplitude of shear strain, that of MSD in the flow direction increases as the amplitude of shear strain is increased, and that the effective diffusion constant depends on both the amplitude and initial phase of the applied sinusoidal shear strains. All experimental results are in good agreement with the theoretical results derived from the Langevin equation. - Itsuki Kunita, Katsuhiko Sato, Yoshimi Tanaka, Yoshinori Takikawa, Hiroshi Orihara, Toshiyuki NakagakiPHYSICAL REVIEW LETTERS 109 (24) 248303 0031-9007 2012/12 [Refereed][Not invited]

We report herein the first evidence that an F-actin solution shows shear banding, which is characterized by the spontaneous separation of homogeneous shear flow into two macroscopic domains of different definite shear rates. The constant shear stress observed in the F-actin solution is explained by the banded flow with volume fractions that obey the lever rule. Nonhomogenous reversible flows were observed in the F-actin solution with respect to upward and downward changes in the shear rate. This is the first time shear banding has been observed in a simple biomacromolecule. The biological implications and dynamic aspects of shear flow velocity characteristic patterns are discussed. - Hiroshi Orihara, Fan Yang, Yuta Takigami, Yoshinori Takikawa, Yang Ho NaPHYSICAL REVIEW E 86 (4) 041701 1539-3755 2012/10 [Refereed][Not invited]

We have investigated the linear response of shear stress to ac electric fields under shear flow in a nematic liquid crystal. The experimental results were compared with the theoretical results derived from the Ericksen-Leslie theory. Although close agreement was obtained at low shear rates, discrepancies were observed at high shear rates. By introducing a two-mode coupling model the experimental results were well reproduced for the entire range of shear rates, and nonconservative forces were found to play an important role in determining the fluctuation dynamics, which is a characteristic of nonequilibrium steady states. - Daiki Endo, Katsuhiko Sato, Yoshinori HayakawaPhysical Review E - Statistical, Nonlinear, and Soft Matter Physics 86 (1) 016106 1539-3755 2012/07/11 [Refereed][Not invited]

We performed experiments to investigate slow fracture in thin rubber films under uniaxial tension using high-viscosity oils. In this system we observed an oscillating instability in slowly propagating cracks for small applied strains. The transition between oscillatory and straight patterns occurred near the characteristic strain at which rubber exhibits a nonlinear stress-strain relation. This suggests that nonlinear elasticity plays an important role in the formation of the observed pattern. This was confirmed by numerical simulation for neo-Hookean and linear elasticity models. © 2012 American Physical Society. - Hiroshi Orihara, Yoshinori TakikawaPHYSICAL REVIEW E 84 (6) 061120.1-061120.5 1539-3755 2011/12 [Not refereed][Not invited]

Brownian motion in a simple shear flow has been experimentally investigated by using a different method for observation and analysis. A number of polystyrene spheres dispersed in sheared water were tracked with a confocal scanning laser microscope, and the time dependences of their coordinates were obtained. Since in the usual mean-square displacement in the flow direction the contribution from the Brownian motion is overwhelmed by that due to the convection, we considered an alternative displacement for which the convection effect could be removed. We found that the new mean-square displacement consists of the normal Einstein diffusion term, which is linear in t, and an anomalous t(3) term arising from the coupling between the diffusion along the velocity gradient and the convection. - Y. Oya, K. Sato, T. KawakatsuEPL 94 (6) 68004 0295-5075 2011/06 [Refereed][Not invited]

Using a field-theoretic approach, we study the equilibrium shape deformation of a vesicle induced by the presence of enclosed flexible polymers. Such a structure can commonly be found in drug delivery systems, endocytosis and polymer/surfactant solutions. To evaluate the total free energy of this system, we combine phase field theory for the membrane and self-consistent field theory for the polymers, and this combination allows us to calculate the bending elastic energy of the membrane, the conformation entropy of the polymers and their interactions simultaneously. Simulations on this coupled model system for axisymmetric shapes show a shape deformation of the vesicle induced by introducing polymers into it. We examined the dependence of the stability of the vesicle shape on the chain length of the polymers and the reduced volume of the vesicle. We present a simple model calculation that shows the relative stability of the prolate shape compared to the oblate shape. Copyright (C) EPLA, 2011 - Katsuhiko Sato, Masako Ohtaki, Yuta Shimamoto, Shin'ichi IshiwataPROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY 105 (3) 199 - 207 0079-6107 2011/05 [Refereed][Not invited]

It is widely accepted that muscle cells take either force-generating or relaxing state in an all-or-none fashion through the so-called excitation-contraction coupling. On the other hand, the membrane-less contractile apparatus takes the third state, i.e., the auto-oscillation (SPOC) state, at the activation level that is intermediate between full activation and relaxation. Here, to explain the dynamics of all three states of muscle, we construct a novel theoretical model based on the balance of forces not only parallel but also perpendicular to the long axis of myofibrils, taking into account the experimental fact that the spacing of myofilament lattice changes with sarcomere length and upon contraction. This theory presents a phase diagram composed of several states of the contractile apparatus and explains the dynamic behavior of SPOC, e.g., periodical changes in sarcomere length with the saw-tooth waveform. The appropriate selection of the constant of the molecular friction due to the cross-bridge formation can explain the difference in the SPOC periods observed under various activating conditions and in different muscle types, i.e., skeletal and cardiac. The theory also predicts the existence of a weak oscillation state at the boundary between SPOC and relaxation regions in the phase diagram. Thus, the present theory comprehensively explains the characteristics of auto-oscillation and contraction in the contractile system of striated muscle. (C) 2010 Elsevier Ltd. All rights reserved. - K. Sato, X. -F. Yuan, T. KawakatsuEUROPEAN PHYSICAL JOURNAL E 31 (2) 135 - 144 1292-8941 2010/02 [Refereed][Not invited]

Numerous numerical and experimental evidence suggest that shear banding behavior looks like first-order phase transitions. In this paper, we demonstrate that this correspondence is actually established in the so-called non-local diffusive Johnson-Segalman model (the DJS model), a typical mechanical constitutive model that has been widely used for describing shear banding phenomena. In the neighborhood of the critical point, we apply the reduction procedure based on the center manifold theory to the governing equations of the DJS model. As a result, we obtain a time evolution equation of the flow field that is equivalent to the time-dependent Ginzburg-Landau (TDGL) equations for modeling thermodynamic first-order phase transitions. This result, for the first time, provides a mathematical proof that there is an analogy between the mechanical instability and thermodynamic phase transition at least in the vicinity of the critical point of the shear banding of DJS model. Within this framework, we can clearly distinguish the metastable branch in the stress-strain rate curve around the shear banding region from the globally stable branch. A simple extension of this analysis to a class of more general constitutive models is also discussed. Numerical simulations for the original DJS model and the reduced TDGL equation is performed to confirm the range of validity of our reduction theory. - Kunihiko Kaneko, Katsuhiko Sato, Tatsuo Michiue, Koji Okabayashi, Kiyoshi Ohnuma, Hiroki Danno, Makoto AsashimaJOURNAL OF EXPERIMENTAL ZOOLOGY PART B-MOLECULAR AND DEVELOPMENTAL EVOLUTION 310B (6) 492 - 503 1552-5007 2008/09 [Refereed][Not invited]

Development is a complex process that involves differentiation into a variety of cell types. In spite of its complexity, the macroscopic pattern and cell types are robust to environmental and developmental perturbations. Even in vitro far from normal developmental conditions, ten normal tissues have been generated from Xenopus animal caps by successive treatment with activin and retinoic acid (RA). To describe both normal development and in vitro organogenesis, we introduce developmental potential following the pioneering Study by Waddington. This potential value represents changeability of a cellular state, which decreases toward a local minimum through development. The attraction to a particular cell type through development is described as a process to decrease the potential value to its local minimum. By choosing an explicit potential form as a function of the concentrations of treated activin and RA, the concentration dependence of in vitro organogenesis is reproduced. The potential landscape is shown to have several local minima, each of which represents a stable cell type. This potential also explains why the induction of given tissues requires more treatment of activin at, later stages. The consequences of the developmental potential hypothesis encompass the robustness of each tissue generation. the loss of competence through development, and the order Of tissues in induction by tissues, which we have confirmed experimentally for in vitro organogenesis. The developmental potential hypothesis for a global description of early development is crucial to understanding the robustness of morphogenesis and explains the achievement of in vitro organogenesis using few molecules as well. - Katsuhiko Sato, Kunihiko KanekoPHYSICAL REVIEW E 75 (6) 061909 1539-3755 2007/06 [Refereed][Not invited]

An equation describing the evolution of phenotypic distribution is derived using methods developed in statistical physics. The equation is solved by using the singular perturbation method, and assuming that the number of bases in the genetic sequence is large. Applying the equation to the mutation-selection model by Eigen provides the critical mutation rate for the error catastrophe. Phenotypic fluctuation of clones (individuals sharing the same gene) is introduced into this evolution equation. With this formalism, it is found that the critical mutation rate is sometimes increased by the phenotypic fluctuations, i.e., noise can enhance robustness of a fitted state to mutation. Our formalism is systematic and general, while approximations to derive more tractable evolution equations are also discussed. - K Sato, K KanekoPHYSICAL BIOLOGY 3 (1) 74 - 82 1478-3967 2006/03 [Refereed][Not invited]

Characterizing a cell state by measuring the degree of gene expression as well as its noise has gathered much attention. The distribution of such state values (e.g., abundances of some proteins) over cells has been measured, and is not only a result of intracellular process, but is also influenced by the growth in cell number that depends on the state. By incorporating the growth-death process into the standard Fokker-Planck equation, a nonlinear temporal evolution equation of distribution is derived and then solved by means of eigenfunction expansions. This general formalism is applied to the linear relaxation case. First, when the growth rate of a cell increases linearly with the state value x, the shift of the average x due to the growth effect is shown to be proportional to the variance of x and the relaxation time, similar to the biological fluctuation-response relationship. Second, when there is a threshold value of x for growth, the existence of a critical growth rate, represented again by the variance and the relaxation time, is demonstrated. The relevance of the results to the analysis of biological data on the distribution of cell states, as obtained for example by flow cytometry, is discussed. - T Yomo, K Sato, Y Ito, K KanekoBIOLOGICALLY INSPIRED APPROACHES TO ADVANCED INFORMATION TECHNOLOGY, PROCEEDINGS 3853 107 - 112 0302-9743 2006 [Refereed][Not invited]

A linear relationship between responses of biological systems and their fluctuations is presented. The fluctuation is given by the variance of a given quantity, whereas the response is given as the average change in the quantity for a given parameter change. By studying experimental evolution where fluorescence per E.coli cell increased, we confirmed our relationship with a positive correlation between the evolutionary rate of fluorescence and its fluctuation observed over genetically identical cells. The generality of the relationship and its possible application to other fluctuating systems are discussed. - K Sato, Y Ito, T Yomo, K KanekoPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 100 (24) 14086 - 14090 0027-8424 2003/11 [Refereed][Not invited]

A general relationship between fluctuation and response in a biological system is presented. The fluctuation is given by the variance of some quantity, whereas the response is given as the average change of that quantity for a given parameter change. We propose a relationship where the two are proportional, in a similar way to the fluctuation-dissipation theorem in physics. By studying an evolution experiment where fluorescence of protein in bacteria increases, we confirm our relation by observing a positive correlation between the speed of fluorescence evolution and the phenotypic fluctuation of the fluorescence over clone bacteria. The generality of the relationship as well as its relevance to evolution is discussed.

- 中垣俊之, 佐藤勝彦, 西上幸範 BSJ-Review 13- 151 2022/08 [Refereed][Invited]
- Kei Hamasaki, Daisuke Takeuchi, Shuji Fujii, Hiroshi Orihara, Katsuhiko Sato, Itsuki Kunita, Kentaro Kayano, Arif Md Rashedul Kabir, Akira Kakugo BIOPHYSICAL JOURNAL 114- (3) 506A -506A 2018/02
- Sato K, Shima S Meeting Abstracts of the Physical Society of Japan 71- (0) 2016 [Not refereed][Not invited]
- Tanaka Yoshimi Meeting Abstracts of the Physical Society of Japan 68- (0) 2013 [Not refereed][Not invited]
- Shin'ichi Ishiwata, Katsuhiko Sato, Masako Ohtaki, Yuta Shimamoto JOURNAL OF PHYSIOLOGICAL SCIENCES 60- S40 -S40 2010 [Not refereed][Not invited]
- T Yomo, Y Ito, K Sato, K Kaneko PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS 350- (1) 1 -5 2005/05 [Not refereed][Not invited]

Do proteins with larger fluctuations in their functions show higher rates of their evolutions? To gain some insight on the question, we conducted an in vitro experimental evolution where a mutant of green fluorescence protein (GFP) with random sequence at its N terminus was subjected to ten cycles of random mutagenesis and selection based On the fluorescence expressed by host Escherichia coli cell. The evolution rate was defined as the fluorescence increase from the parental clone to the selected clone at each generation and the fluctuation was defined as the variance in green fluorescence among the host cells of the parental clone Lit each generation. The analysis of the relationship between the evolution rate and the fluctuation based on fluctuation-dissipation theorem in statistical physics shows that the gene or encoded protein rendering a larger fluctuation of the fluorescence shows a larger evolution rate, i.e., positive correlation between fluctuation and molecular evolution rate. (c) 2004 Elsevier B.V. All rights reserved. - 2M1345 Experimental study on the relationship between flexibility of bio-organismsand evolution rateIto Y., Ito K., Kaneko K., Yomo T. Seibutsu Butsuri 42- (2) S137 2002/10/10 [Not refereed][Not invited]