Laboratory of Structural Biophysics and Mechanobiology, The Rockefeller University, New York, NY, USA.
FEBS J. 2023 May;290(10):2576-2589. doi: 10.1111/febs.16568. Epub 2022 Jul 13.
The actin cytoskeleton orchestrates cell mechanics and facilitates the physical integration of cells into tissues, while tissue-scale forces and extracellular rigidity in turn govern cell behaviour. Here, we discuss recent evidence that actin filaments (F-actin), the core building blocks of the actin cytoskeleton, also serve as molecular force sensors. We delineate two classes of proteins, which interpret forces applied to F-actin through enhanced binding interactions: 'mechanically tuned' canonical actin-binding proteins, whose constitutive F-actin affinity is increased by force, and 'mechanically switched' proteins, which bind F-actin only in the presence of force. We speculate mechanically tuned and mechanically switched actin-binding proteins are biophysically suitable for coordinating cytoskeletal force-feedback and mechanical signalling processes, respectively. Finally, we discuss potential mechanisms mediating force-activated actin binding, which likely occurs both through the structural remodelling of F-actin itself and geometric rearrangements of higher-order actin networks. Understanding the interplay of these mechanisms will enable the dissection of force-activated actin binding's specific biological functions.
肌动蛋白细胞骨架协调细胞力学并促进细胞与组织的物理整合，而组织尺度的力和细胞外刚度反过来又控制细胞行为。在这里，我们讨论了最近的证据表明，肌动蛋白丝（F-肌动蛋白）是肌动蛋白细胞骨架的核心组成部分，也作为分子力传感器。我们描述了两类蛋白质，它们通过增强的结合相互作用来解释施加在 F-肌动蛋白上的力：“机械调谐”的经典肌动蛋白结合蛋白，其 F-肌动蛋白亲和力通过力增加，以及“机械切换”蛋白，仅在存在力的情况下结合 F-肌动蛋白。我们推测机械调谐和机械切换的肌动蛋白结合蛋白分别在协调细胞骨架力反馈和机械信号转导过程方面具有生物物理适宜性。最后，我们讨论了介导力激活肌动蛋白结合的潜在机制，这可能通过 F-肌动蛋白本身的结构重塑和高阶肌动蛋白网络的几何重排来发生。了解这些机制的相互作用将能够剖析力激活肌动蛋白结合的特定生物学功能。
