細胞力学研究を振り返って

抄録

The author has continued to research on cytomechanics since 1983 when he visited Professor Nerem’s laboratory, University of Houston, Texas, USA as a visiting scholar. In those days the effects of shear stress on functions of endothelial cells (EC) are focused from the point of view of atherogenesis. In this review, progress of cytomechanics on EC is mainly summarized. First, the definition and the significance of cytomechanics are introduced. EC are located at the innermost layer of vascular wall and always exposed to three different external forces (i.e. shear stress, cyclic stretch and hydrostatic pressure). These mechanical forces affect the configuration and functions of EC and the cells finally adapt a physical environment. Cultured EC elongates and aligns to direction of flow and the degree of shape change depends on many factors such as animal and cell species, magnitude of shear stress, duration of stimulation, material of substrate and so on. Cytoskeletal structure is also changed prior to change of cell shape. Cyclic stretch induces cell elongation and the orientation transversely to the strain direction. Pressured EC exhibit multilayered structure and marked elongation and orientation with the random direction, together with development of centrally located, thick stress fibers. Mechanical forces stimulate signal transduction, gene regulation, protein synthesis and so on. The details of the time course of responses is summarized in the text. Recent progresses on cytomechanics are two topics as follows. One is an effect of substrate elasticity on differentiation of stem cells. Human mesenchymal stem cells are cultured on three different elastic substrate (i.e. soft, moderate and stiff matrices), and then respectively differentiated into neuron, muscle and bone. Another is discovery of mechanosensing molecule called mechanosensor. Living cells respond to external and internal forces, however, the sensing mechanism is not elucidated yet. Mechanosensors such as stretch-activated channel in cell membrane, p130Cas, α-catenin, talin at cell junctions and stress fiber itself are explained as the typical examples.