Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiovascular Medicine, Yale University, New Haven, CT 06511.
Department of Chemical and Biomedical Engineering, Florida A&M University-Florida State University College of Engineering, Tallahassee, FL 32310.
Proc Natl Acad Sci U S A. 2020 Dec 22;117(51):32413-32422. doi: 10.1073/pnas.2010292117. Epub 2020 Dec 1.
Integrin-dependent adhesions mediate reciprocal exchange of force and information between the cell and the extracellular matrix. These effects are attributed to the "focal adhesion clutch," in which moving actin filaments transmit force to integrins via dynamic protein interactions. To elucidate these processes, we measured force on talin together with actin flow speed. While force on talin in small lamellipodial adhesions correlated with actin flow, talin tension in large adhesions further from the cell edge was mainly flow-independent. Stiff substrates shifted force transfer toward the flow-independent mechanism. Flow-dependent force transfer required talin's C-terminal actin binding site, ABS3, but not vinculin. Flow-independent force transfer initially required vinculin and at later times the central actin binding site, ABS2. Force transfer through integrins thus occurs not through a continuous clutch but through a series of discrete states mediated by distinct protein interactions, with their ratio modulated by substrate stiffness.
整合素依赖性黏附介导细胞与细胞外基质之间力和信息的相互交换。这些效应归因于“黏附点离合器”，其中移动的肌动蛋白丝通过动态蛋白相互作用将力传递给整合素。为了阐明这些过程，我们测量了 talin 上的力以及肌动蛋白流速。虽然在小片状伪足黏附中的 talin 上的力与肌动蛋白流速相关，但远离细胞边缘的大黏附中的 talin 张力主要与流速无关。刚性基底将力传递转移到与流速无关的机制。依赖流速的力传递需要 talin 的 C 末端肌动蛋白结合位点 ABS3，但不需要 vinculin。流速无关的力传递最初需要 vinculin，而在稍后的时间需要中央肌动蛋白结合位点 ABS2。因此，整合素中的力传递不是通过连续的离合器，而是通过一系列由不同蛋白相互作用介导的离散状态发生的，其比例由基底刚度调节。
