Cell Mechanics at the Rear Act to Steer the Direction of Cell Migration.
Cell Mechanics at the Rear Act to Steer the Direction of Cell Migration.
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DOI：
10.1016/j.cels.2020.08.008
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发表时间：
2020-09-23
期刊：
影响因子：
9.3
通讯作者：
Mogilner A
中科院分区：
文献类型：
--
作者：
Allen GM;Lee KC;Barnhart EL;Tsuchida MA;Wilson CA;Gutierrez E;Groisman A;Theriot JA;Mogilner A
运动细胞通过改变它们的行进方向来导航复杂的环境，在它们的机械子系统中产生左右不对称以物理地转向。目前很少有人知道外部的方向性线索是如何传播沿着整个细胞的长度尺度，并与其力产生装置整合，以引导迁移机械。我们研究了鱼类表皮角质形成细胞自发细胞转动的机制，发现负责转动行为的机械不对称性在细胞后部占主导地位，那里有不对称的向心肌动蛋白流。使用实验扰动，我们确定了两个链接的反馈回路连接肌球蛋白II收缩性，粘附强度和肌动蛋白网络流在转向细胞，足以解释所观察到的细胞形状和轨迹。值得注意的是，在细胞前沿的肌动蛋白聚合的不对称性在细胞转向的力学中只起很小的作用-也就是说，细胞从后面转向。运动细胞必须能够转向以适应复杂的环境。目前，人们对允许细胞转动的机械作用知之甚少。我们研究了鱼类表皮角化细胞自发细胞转动的机制，发现负责转动行为的不对称性在细胞后部占主导地位。我们发现，当细胞转动时，与肌动蛋白细胞骨架结合的肌球蛋白被扫到细胞的外侧，在那里它的作用是局部增加肌动蛋白细胞骨架的收缩，并减弱细胞对细胞沿着爬行的表面的粘附。这些机械力导致外部细胞翼移动得更快并驱动转向。在转向细胞的相对内侧，肌球蛋白相对稀疏，导致肌动蛋白收缩减少，并导致细胞与表面的强粘附。从本质上讲，细胞粘在一边，滑到另一边，旋转成一个转弯。这些相互联系的反馈回路连接肌球蛋白收缩性，粘附强度和肌动蛋白网络流动的转向细胞是足以解释所观察到的细胞转向。值得注意的是，在细胞前沿的肌动蛋白聚合的不对称性在细胞转向的力学中只起很小的作用-也就是说，细胞从后面转向。
Motile cells navigate complex environments by changing their direction of travel, generating left-right asymmetries in their mechanical subsystems to physically turn. Currently little is known about how external directional cues are propagated along the length scale of the whole cell and integrated with its force-generating apparatus to steer migration mechanically. We examine the mechanics of spontaneous cell turning in fish epidermal keratocytes and find that the mechanical asymmetries responsible for turning behavior predominate at the rear of the cell, where there is asymmetric centripetal actin flow. Using experimental perturbations, we identify two linked feedback loops connecting myosin II contractility, adhesion strength and actin network flow in turning cells that are sufficient to explain the observed cell shapes and trajectories. Notably, asymmetries in actin polymerization at the cell leading edge play only a minor role in the mechanics of cell turning – that is, cells steer from the rear. Motile cells must be able to turn to navigate complex environments. Currently, little is known about mechanical actions that allow a cell to turn. We examine the mechanics of spontaneous cell turning in fish epidermal keratocytes and find that asymmetries responsible for turning behavior predominate at the rear of the cell. We find that as a cell turns myosin, bound to the actin cytoskeleton, is swept to the outer side of the cell where it acts to locally increase contraction of the actin cytoskeleton and weaken cellular adhesion to the surface that the cell crawls along. These mechanical forces lead to the outer cell wing to move faster and drive turning. On the opposing inner side of the turning cell, myosin is relatively sparse leading to a reduction in the contraction of actin and to strong cellular adhesion to the surface. Essentially, the cell sticks on one side and slips on the other, pivoting into a turn. These interlinked feedback loops connecting myosin contractility, adhesion strength and actin network flow in turning cells are sufficient to explain the observed cell turning. Notably, asymmetries in actin polymerization at the cell leading edge play only a minor role in the mechanics of cell turning – that is, cells steer from the rear.
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影响因子：
7.8
作者：
Gardel, Margaret L.;Sabass, Benedikt;Ji, Lin;Danuser, Gaudenz;Schwarz, Ulrich S.;Waterman, Clare M.
通讯作者：
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