Institute for Frontier Medical Science, Kyoto University
Yasuhiro Inoue (Cell Scale WG)
The actin cytoskeleton forms higher structures such as a network structure and bundle structure through interaction of various auxiliary proteins using actin filaments as the basic skeleton, in which actin monomers are coupled with one another, and constitutes an important mechanical and chemical base which supports cell shape and motion. For example, actin beneath the cell surface forms structures for motility such as filopodia and lamellipodia. They are essential for formation of neuronal growth cone and cell motion. In actomyosin filaments consisting of actin and myosin, the motor motion of myosin generates a force, which is crucial in cell deformation in morphogenesis, cytoplasmic division by a contractile ring, and turnover of cell adhesion. Those structures emerge from molecular systems centered on actin, and can change their structures and characteristics dynamically by going the round of mechanically and chemically metastable states. We are studying the relation of actin cytoskeleton dynamics to cell functions by using a computational mechanobiology approach. Our recent studies revealed that cell shape in cell motion is coupled with actin polymerization via thermal fluctuation , and the relation between the force generated in the actomyosin network and the myosin density is bilinear in response to network structure change . These studies give important insights in the relation between cell-scale expression of function and molecularscale dynamics. Since actin mechanobiology can be simulated by using computers, it is not a totally unrealizable dream to recreate a whole cell on the computer. Of course, we have a lot of challenges to overcome. As for these challenges, we have to work with researchers inside and outside the Next-Generation Integrated Simulation of Living Matter Group. A Computational Science Algorithm Study Group is regularly held to create such an opportunity. There, researchers share knowledge of mathematical models and computational approaches beyond the scope of their fields, and pursue collaboration with researchers in related boundary areas.
 Inoue, Y and Adachi, T. Biomech. Model. Mechanobiol. 2011 10:495-503
 Inoue, Y. Tsuda, S., Nakagawa K., Hojo, M., Adachi T. J Theor Biol. 2011 21;281(1):65-73
Fig 1 : Computational simulation of migrant cell: Cell shape obtained by simulation (solid line) coincides with actually-observed cell shape (fluorescence image). In addition, it was found that the actin polymerization speed at the tip of the cell (longitudinal axis) is in proportion to the curvature radius at the tip of the cell (horizontal axis).
Fig 2 : Autonomous structural change of actomyosin net work : Due to motor motion of myosin in the actomyosin net work, the struc ture of ac tomyosin network changes autonomously. Simulation showed that the force generated in the network according to restructuring is bilinear with respect to myosin density.