Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland, USA.
Biophys J. 2012 Jan 18;102(2):201-10. doi: 10.1016/j.bpj.2011.12.022.
In hair cells, although mechanotransduction channels have been localized to tips of shorter stereocilia of the mechanically sensitive hair bundle, little is known about how force is transmitted to the channel. Here, we use a biophysical model of the membrane-channel complex to analyze the nature of the gating spring compliance and channel arrangement. We use a triangulated surface model and Monte Carlo simulation to compute the deformation of the membrane under the action of tip link force. We show that depending on the gating spring stiffness, the compliant component of the gating spring arises from either the membrane alone or a combination of the membrane and a tether that connects the channel to the actin cytoskeleton. If a bundle is characterized by relatively soft gating springs, such as those of the bullfrog sacculus, the need for membrane reinforcement by channel tethering then depends on membrane parameters. With stiffer gating springs, such as those from rat outer hair cells, the channel must be tethered for all biophysically realistic parameters of the membrane. We compute the membrane forces (resultants), which depend on membrane tension, bending modulus, and curvature, and show that they can determine the fate of the channel.
在毛细胞中,尽管机械转导通道已被定位到机械敏感毛束较短的静纤毛的顶端,但对于力如何传递到通道知之甚少。在这里,我们使用膜通道复合物的生物物理模型来分析门控弹簧顺应性和通道排列的性质。我们使用三角曲面模型和蒙特卡罗模拟来计算膜在顶链接力作用下的变形。我们表明,根据门控弹簧的刚度,门控弹簧的顺应性组件要么来自膜本身,要么来自将通道连接到肌动球蛋白细胞骨架的系链的组合。如果纤毛束的门控弹簧相对较软,例如牛蛙囊的门控弹簧,则通过通道系链增强膜的必要性取决于膜参数。对于更硬的门控弹簧,例如大鼠外毛细胞的门控弹簧,对于膜的所有生物物理现实参数,通道必须被系链。我们计算了取决于膜张力、弯曲模量和曲率的膜力(合力),并表明它们可以决定通道的命运。