Sensing substrate rigidity by mechanosensitive ion channels with stress fibers and focal adhesions

Cell motility, spreading, proliferation and differentiation are critically influenced by substrate rigidity. To sense substrate rigidity, cells apply traction forces to cell-substrate adhesions via actin stress fibers (SFs) and measure mechanical responses of the substrate. Besides mechanosensitive adaptor proteins, mechanosensitive (MS) channels are involved in the substrate rigidity sensing. MS channels located at or near focal adhesions (FAs) convert the rigidity-dependent stress generated in SF/FA system into the level of cytoplasmic Ca2+ concentration ([Ca2+]cyt) by locally altering their Ca2+ permeability. Besides by external forces, cells spontaneously generate rigidity-dependent localized [Ca2+]cyt increases, implicating MS channels as intrinsic force measurement system. This mechanism may contribute to not only substrate rigidity sensing but also regulation of cell migration.