Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute.
Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell. 2018 Dec 13;175(7):1769-1779.e13. doi: 10.1016/j.cell.2018.09.054. Epub 2018 Nov 1.
The fluid-mosaic model posits a liquid-like plasma membrane, which can flow in response to tension gradients. It is widely assumed that membrane flow transmits local changes in membrane tension across the cell in milliseconds, mediating long-range signaling. Here, we show that propagation of membrane tension occurs quickly in cell-attached blebs but is largely suppressed in intact cells. The failure of tension to propagate in cells is explained by a fluid dynamical model that incorporates the flow resistance from cytoskeleton-bound transmembrane proteins. Perturbations to tension propagate diffusively, with a diffusion coefficient D ∼0.024 μm/s in HeLa cells. In primary endothelial cells, local increases in membrane tension lead only to local activation of mechanosensitive ion channels and to local vesicle fusion. Thus, membrane tension is not a mediator of long-range intracellular signaling, but local variations in tension mediate distinct processes in sub-cellular domains.
流动镶嵌模型假设质膜为液态,能响应张力梯度而流动。人们普遍认为,质膜流动能在毫秒级时间内将细胞膜张力的局部变化传递到细胞中,从而介导长距离信号转导。本文中,我们发现,细胞贴附泡中的膜张力快速传播,但在完整细胞中,这种传播则受到很大抑制。该流动镶嵌模型表明,质膜张力无法在细胞中传播,其原因在于跨膜蛋白与细胞骨架结合导致的流动阻力。该模型还解释了张力波动的扩散性,在 HeLa 细胞中,扩散系数 D∼0.024 μm/s。在原代内皮细胞中,膜张力的局部增加仅导致机械敏感离子通道的局部激活和局部囊泡融合。因此,膜张力不是长距离细胞内信号转导的介质,而是局部张力变化在亚细胞域中介导不同的过程。
Cell. 2018-11-1
Bioessays. 2020-1
Nat Chem. 2018-8-27
J Biol Chem. 2003-12-12
Biophys J. 2015-4-7
PRX Life. 2024
J Cell Sci. 2025-8-15
Research (Wash D C). 2025-8-13
Proc Natl Acad Sci U S A. 2025-5-13
Biophys J. 2025-3-4
Philos Trans R Soc Lond B Biol Sci. 2018-5-26
J Cell Sci. 2018-2-22
Nature. 2017-12-20
Neurosci Res. 2018-2
Cell. 2017-8-31
Semin Cell Dev Biol. 2017-8-26
Nat Rev Immunol. 2017-11