Molecular basis of mechanotransduction in living cells

The simplest cell-like structure, the lipid bilayer vesicle, can respond to mechanical deformation by elastic membrane dilation/thinning and curvature changes. When a protein is inserted in the lipid bilayer, an energetic cos t may arise because of hydrophobic mismatch between the protein and bilayer . Localized changes in bilayer thickness and curvature may compensate for t his mismatch. The peptides alamethicin and gramicidin and the bacterial mem brane protein MscL form mechanically gated (MG) channels when inserted in l ipid bilayers. Their mechanosensitivity may arise because channel opening i s associated with a change in the protein's membrane-occupied area, its hyd rophobic mismatch with the bilayer, excluded water volume, or a combination of these effects. As a consequence, bilayer dilation/thinning or changes i n local membrane curvature may shift the equilibrium between channel confor mations. Recent evidence indicates that MG channels in specific animal cell types (e.g., Xenopus oocytes) are also gated directly by bilayer tension. However, animal cells lack the rigid cell wall that protects bacteria and p lants cells from excessive expansion of their bilayer. Instead, a cortical cytoskeleton (CSK) provides a structural framework that allows the animal c ell to maintain a stable excess membrane area (i.e., for its volume occupie d by a sphere) in the form of membrane folds, ruffles, and microvilli. This excess membrane provides an immediate membrane reserve that may protect th e bilayer from sudden changes in bilayer tension. Contractile elements with in the CSK may locally slacken or tighten bilayer tension to regulate mecha nosensitivity, whereas membrane blebbing and tight seal patch formation, by using up membrane reserves, may increase membrane mechanosensitivity. In s pecific cases, extracellular and/or CSK proteins (i.e., tethers) may transm it mechanical forces to the process (e.g., hair cell MG channels, MS intrac ellular Ca2+ release, and transmitter release) without increasing tension i n the Lipid bilayer.