Coupling during collective cell migration is controlled by a vinculin mechanochemical switch.
Coupling during collective cell migration is controlled by a vinculin mechanochemical switch.
复制标题
集体细胞迁移期间的耦合由纽蛋白机械化学开关控制。
DOI：
10.1073/pnas.2316456120
复制
发表时间：
2023
影响因子：
11.1
通讯作者：
Hoffman,BrentonD
中科院分区：
文献类型：
--
作者：
Shoyer,TCurtis;Gates,EvanM;Cabe,JoleneI;Urs,AartiN;Conway,DanielE;Hoffman,BrentonD
细胞以机械耦合、协调的方式移动的能力，称为集体细胞迁移，是许多发育、生理和病理生理过程的核心。对机械力和生化调节如何相互作用以影响耦合的有限理解一直是解开潜在机制的主要障碍。聚焦于连接蛋白vinculin，我们使用一套基于Förster共振能量转移的生物传感器来探测其机械功能和生化调节，揭示了一个开关，该开关将vinculin在非稳态和非稳态之间切换。开关的扰动导致细胞速度和协调的共变变化，表明系统内摩擦的改变。分子尺度模型显示，由于自稳定捕获键的接合，增加水平的黏着斑蛋白增加摩擦。总之，这项工作揭示了一个控制细胞耦合的调节开关，并描述了一个有关生化调节，改变机械性能和细胞行为变化的范例。
The ability of cells to move in a mechanically coupled, coordinated manner, referred to as collective cell migration, is central to many developmental, physiological, and pathophysiological processes. Limited understanding of how mechanical forces and biochemical regulation interact to affect coupling has been a major obstacle to unravelling the underlying mechanisms. Focusing on the linker protein vinculin, we use a suite of Förster resonance energy transfer-based biosensors to probe its mechanical functions and biochemical regulation, revealing a switch that toggles vinculin between loadable and unloadable states. Perturbation of the switch causes covarying changes in cell speed and coordination, suggesting alteration of the friction within the system. Molecular scale modelling reveals that increasing levels of loadable vinculin increases friction, due to engagement of self-stabilizing catch bonds. Together, this work reveals a regulatory switch for controlling cell coupling and describes a paradigm for relating biochemical regulation, altered mechanical properties, and changes in cell behaviors.