The actin cytoskeleton mediates mechanical coupling between cells and their tissue microenvironments. The architecture and composition of actin networks are modulated by force; however, it is unclear how interactions between actin filaments (F-actin) and associated proteins are mechanically regulated. Here we employ both optical trapping and biochemical reconstitution with myosin motor proteins to show single piconewton forces applied solely to F-actin enhance binding by the human version of the essential cell-cell adhesion protein αE-catenin but not its homolog vinculin. Cryo-electron microscopy structures of both proteins bound to F-actin reveal unique rearrangements that facilitate their flexible C-termini refolding to engage distinct interfaces. Truncating α-catenin’s C-terminus eliminates force-activated F-actin binding, and addition of this motif to vinculin confers force-activated binding, demonstrating that α-catenin’s C-terminus is a modular detector of F-actin tension. Our studies establish that piconewton force on F-actin can enhance partner binding, which we propose mechanically regulates cellular adhesion through α-catenin.

中文翻译：

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α-连环蛋白直接肌动蛋白力传感的分子机制

肌动蛋白细胞骨架介导细胞与其组织微环境之间的机械耦合。肌动蛋白网络的结构和组成受力调节；然而，尚不清楚肌动蛋白丝（F-肌动蛋白）和相关蛋白质之间的相互作用是如何机械调节的。在这里，我们使用肌球蛋白运动蛋白进行光学捕获和生化重建，以显示仅应用于 F-肌动蛋白的单个皮牛顿力增强了人类版本的基本细胞 - 细胞粘附蛋白 αE-连环蛋白的结合，但不是其同源蛋白。与 F-肌动蛋白结合的两种蛋白质的冷冻电子显微镜结构揭示了独特的重排，有助于其灵活的 C 端重新折叠以接合不同的界面。截断 α-连环蛋白的 C 端消除了强制激活的 F-肌动蛋白结合，并且将这个基序添加到纽蛋白赋予力激活结合，证明 α-连环蛋白的 C 端是 F-肌动蛋白张力的模块化检测器。我们的研究确定 F-肌动蛋白上的皮牛顿力可以增强伴侣结合，我们建议通过 α-连环蛋白机械调节细胞粘附。