Hamill O P, Martinac B
Physiology and Biophysics, University Of Texas Medical Branch, Galveston, Texas 77555, USA.
Physiol Rev. 2001 Apr;81(2):685-740. doi: 10.1152/physrev.2001.81.2.685.
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 cost may arise because of hydrophobic mismatch between the protein and bilayer. Localized changes in bilayer thickness and curvature may compensate for this mismatch. The peptides alamethicin and gramicidin and the bacterial membrane protein MscL form mechanically gated (MG) channels when inserted in lipid bilayers. Their mechanosensitivity may arise because channel opening is associated with a change in the protein's membrane-occupied area, its hydrophobic mismatch with the bilayer, excluded water volume, or a combination of these effects. As a consequence, bilayer dilation/thinning or changes in local membrane curvature may shift the equilibrium between channel conformations. 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 plants cells from excessive expansion of their bilayer. Instead, a cortical cytoskeleton (CSK) provides a structural framework that allows the animal cell to maintain a stable excess membrane area (i.e., for its volume occupied by a sphere) in the form of membrane folds, ruffles, and microvilli. This excess membrane provides an immediate membrane reserve that may protect the bilayer from sudden changes in bilayer tension. Contractile elements within the CSK may locally slacken or tighten bilayer tension to regulate mechanosensitivity, whereas membrane blebbing and tight seal patch formation, by using up membrane reserves, may increase membrane mechanosensitivity. In specific cases, extracellular and/or CSK proteins (i.e., tethers) may transmit mechanical forces to the process (e.g., hair cell MG channels, MS intracellular Ca(2+) release, and transmitter release) without increasing tension in the lipid bilayer.
最简单的细胞样结构，即脂质双分子层囊泡，可通过弹性膜扩张/变薄和曲率变化来响应机械变形。当一种蛋白质插入脂质双分子层时，由于蛋白质与双分子层之间的疏水不匹配，可能会产生能量消耗。双分子层厚度和曲率的局部变化可补偿这种不匹配。短杆菌肽A和短杆菌肽以及细菌膜蛋白MscL插入脂质双分子层时会形成机械门控（MG）通道。它们的机械敏感性可能源于通道开放与蛋白质在膜中所占面积的变化、其与双分子层的疏水不匹配、排除的水量或这些效应的组合有关。因此，双分子层扩张/变薄或局部膜曲率的变化可能会改变通道构象之间的平衡。最近的证据表明，特定动物细胞类型（如非洲爪蟾卵母细胞）中的MG通道也直接受双分子层张力门控。然而，动物细胞缺乏保护细菌和植物细胞免受其双分子层过度扩张影响的刚性细胞壁。相反，皮质细胞骨架（CSK）提供了一个结构框架，使动物细胞能够以膜褶皱、波纹和微绒毛的形式维持稳定的过量膜面积（即对于其被球体占据的体积而言）。这种过量的膜提供了即时的膜储备，可保护双分子层免受双分子层张力的突然变化影响。CSK内的收缩元件可能会局部放松或收紧双分子层张力以调节机械敏感性，而膜泡形成和紧密密封斑形成通过消耗膜储备可能会增加膜机械敏感性。在特定情况下，细胞外和/或CSK蛋白（即系链）可能会将机械力传递给该过程（如毛细胞MG通道、MS细胞内Ca(2+)释放和递质释放），而不会增加脂质双分子层中的张力。
