Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland.
Department of Microbiology, Columbia University, New York, New York.
Biophys J. 2014 Jun 3;106(11):2519-28. doi: 10.1016/j.bpj.2014.03.034.
In hair cells, mechanotransduction channels are located in the membrane of stereocilia tips, where the base of the tip link is attached. The tip-link force determines the system of other forces in the immediate channel environment, which change the channel open probability. This system of forces includes components that are out of plane and in plane relative to the membrane; the magnitude and direction of these components depend on the channel environment and arrangement. Using a computational model, we obtained the major forces involved as functions of the force applied via the tip link at the center of the membrane. We simulated factors related to channels and the membrane, including finite-sized channels located centrally or acentrally, stiffness of the hypothesized channel-cytoskeleton tether, and bending modulus of the membrane. Membrane forces are perpendicular to the directions of the principal curvatures of the deformed membrane. Our approach allows for a fine vectorial picture of the local forces gating the channel; membrane forces change with the membrane curvature and are themselves sufficient to affect the open probability of the channel.
在毛细胞中,机械转导通道位于静纤毛尖端的膜上,而尖端连接的底部附着在该处。尖端连接力决定了紧邻通道环境中的其他力系统,这些力系统会改变通道的开放概率。这个力系统包括相对于膜平面内外的组成部分;这些组成部分的大小和方向取决于通道环境和排列。我们使用计算模型,将主要涉及的力作为通过膜中心的尖端连接施加的力的函数来获得。我们模拟了与通道和膜相关的因素,包括位于中心或偏心位置的有限大小的通道、假设的通道-细胞骨架系绳的刚度以及膜的弯曲模量。膜力垂直于变形膜的主曲率方向。我们的方法允许对局部力进行精细的向量描述,从而控制通道;膜力随膜曲率而变化,并且足以影响通道的开放概率。