Integrin-mediated mechanosensing of the extracellular environment allows cells to control adhesion and signalling. Whether cells sense and respond to force immediately upon ligand-binding is unknown. Here, we report that during adhesion initiation, fibroblasts respond to mechanical load by strengthening integrin-mediated adhesion to fibronectin (FN) in a biphasic manner. In the first phase, which depends on talin and kindlin as well as on the actin nucleators Arp2/3 and mDia, FN-engaged α5β1 integrins activate focal adhesion kinase (FAK) and c-Src in less than 0.5 s to steeply strengthen α5β1- and αV-class integrin-mediated adhesion. When the mechanical load exceeds a certain threshold, fibroblasts decrease adhesion and initiate the second phase, which is characterized by less steep adhesion strengthening. This unique, biphasic cellular adhesion response is mediated by α5β1 integrins, which form catch bonds with FN and signal to FN-binding integrins to reinforce cell adhesion much before visible adhesion clusters are formed.

中文翻译：

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纤连蛋白结合的α5β1整合素在不到一秒钟的时间内感测到负荷并发出信号以增强粘附力

整联蛋白介导的细胞外环境机械传感使细胞能够控制粘附和信号传导。细胞是否能在配体结合后立即感知力并对其作出反应尚不清楚。在这里，我们报告说，在粘附启动过程中，成纤维细胞通过增强整联蛋白介导的对纤连蛋白（FN）的双相粘附来响应机械负荷。在第一阶段，这取决于踝蛋白和kindlin以及对肌动蛋白成核的Arp2 / 3和MDIA，FN-接合α 5β1整合素激活粘着斑激酶（FAK）和c-Src的在小于0.5 为s急剧加强α 5β1-和αV级整联蛋白介导的粘附。当机械负荷超过一定阈值时，成纤维细胞降低粘附力并开始第二阶段，第二阶段的特征是陡峭的粘附强度增强。这种独特的，双相的细胞粘附反应是由介导的α 5β1整合素，形式捕捉债券FN和信号FN结合整联，以加强形成可见粘附簇多前细胞粘附这。