Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT
Department of Biology, University of Pennsylvania, Philadelphia, PA.
J Cell Biol. 2019 Aug 5;218(8):2481-2491. doi: 10.1083/jcb.201901086. Epub 2019 Jul 17.
Cell sensing of externally applied mechanical strain through integrin-mediated adhesions is critical in development and physiology of muscle, lung, tendon, and arteries, among others. We examined the effects of strain on force transmission through the essential cytoskeletal linker talin. Using a fluorescence-based talin tension sensor (TS), we found that uniaxial stretch of cells on elastic substrates increased tension on talin, which was unexpectedly independent of the orientation of the focal adhesions relative to the direction of strain. High-resolution electron microscopy of the actin cytoskeleton revealed that stress fibers (SFs) are integrated into an isotropic network of cortical actin filaments in which filamin A (FlnA) localizes preferentially to points of intersection between SFs and cortical actin. Knockdown (KD) of FlnA resulted in more isolated, less integrated SFs. After FlnA KD, tension on talin was polarized in the direction of stretch, while FlnA reexpression restored tensional symmetry. These data demonstrate that a FlnA-dependent cortical actin network distributes applied forces over the entire cytoskeleton-matrix interface.
细胞通过整合素介导的黏附感知外部施加的机械应变，这在肌肉、肺、肌腱和动脉等组织的发育和生理过程中至关重要。我们研究了应变对必需的细胞骨架接头蛋白talin 传递力的影响。使用基于荧光的 talin 张力传感器 (TS)，我们发现细胞在弹性基质上的单轴拉伸增加了 talin 的张力，这令人意外地与黏附点相对于应变方向的取向无关。对肌动蛋白细胞骨架的高分辨率电子显微镜观察显示，应力纤维 (SF) 整合到皮层肌动蛋白丝的各向同性网络中，其中细丝蛋白 A (FlnA) 优先定位于 SF 与皮层肌动蛋白的交叉点。FlnA 的敲低 (KD) 导致 SF 更加孤立，集成度更低。在 FlnA KD 后，talin 的张力在拉伸方向上极化，而 FlnA 的重新表达恢复了张力的对称性。这些数据表明，FlnA 依赖性皮层肌动蛋白网络将施加的力分布在整个细胞骨架-基质界面上。
