The force loading rate drives cell mechanosensing through both reinforcement and cytoskeletal softening.
The force loading rate drives cell mechanosensing through both reinforcement and cytoskeletal softening.
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DOI：
10.1038/s41467-021-24383-3
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发表时间：
2021-07-09
影响因子：
16.6
通讯作者：
Roca-Cusachs P
中科院分区：
文献类型：
--
作者：
Andreu I;Falcones B;Hurst S;Chahare N;Quiroga X;Le Roux AL;Kechagia Z;Beedle AEM;Elosegui-Artola A;Trepat X;Farré R;Betz T;Almendros I;Roca-Cusachs P
细胞对力的反应调节着健康和疾病的基本过程。然而，细胞感知和反应的基本机械变量仍不清楚。在这里，我们展示了力施加的速率（加载速率）驱动机械传感，正如分子离合器模型所预测的那样。通过基底拉伸、光学镊子和原子力显微镜对细胞施加动态力，我们发现增加加载率会触发依赖于taln的机械传感，导致粘附生长和增强，以及YAP核定位。然而，超过一个给定的阈值，肌动蛋白细胞骨架软化，降低负载率和防止加固。通过在体内拉伸大鼠肺，我们发现可能会发生类似的现象。我们的研究结果表明，细胞对外力和被动机械参数（如组织刚度）的感知可以通过相同的机制来理解，由所涉及的机械感知分子的受力特性驱动。细胞从环境中感知机械力，但细胞感知的精确机械变量尚不清楚。在这里，作者表明细胞可以感知力的施加速率，即加载速率，对YAP核定位和细胞骨架刚度重塑产生影响。
Cell response to force regulates essential processes in health and disease. However, the fundamental mechanical variables that cells sense and respond to remain unclear. Here we show that the rate of force application (loading rate) drives mechanosensing, as predicted by a molecular clutch model. By applying dynamic force regimes to cells through substrate stretching, optical tweezers, and atomic force microscopy, we find that increasing loading rates trigger talin-dependent mechanosensing, leading to adhesion growth and reinforcement, and YAP nuclear localization. However, above a given threshold the actin cytoskeleton softens, decreasing loading rates and preventing reinforcement. By stretching rat lungs in vivo, we show that a similar phenomenon may occur. Our results show that cell sensing of external forces and of passive mechanical parameters (like tissue stiffness) can be understood through the same mechanisms, driven by the properties under force of the mechanosensing molecules involved. Cells sense mechanical forces from their environment, but the precise mechanical variable sensed by cells is unclear. Here, the authors show that cells can sense the rate of force application, known as the loading rate, with effects on YAP nuclear localization and cytoskeletal stiffness remodelling.
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影响因子：
16.6
作者：
Chaudhuri O;Gu L;Darnell M;Klumpers D;Bencherif SA;Weaver JC;Huebsch N;Mooney DJ
通讯作者：
Mooney DJ
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：
Waterman, Clare M.
DOI：
10.1038/nrm3112
发表时间：
2011-05
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.0806085105
发表时间：
2008-10-14
影响因子：
11.1
作者：
Dudko, Olga K.;Hummer, Gerhard;Szabo, Attila
通讯作者：
Szabo, Attila
影响因子：
3.4
作者：
Evans, E;Ritchie, K
通讯作者：
Ritchie, K