Choquet D, Felsenfeld D P, Sheetz M P
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Cell. 1997 Jan 10;88(1):39-48. doi: 10.1016/s0092-8674(00)81856-5.
To move forward, migrating cells must generate traction forces through surface receptors bound to extracellular matrix molecules coupled to a rigid structure. We investigated whether cells sample and respond to the rigidity of the anchoring matrix. Movement of beads coated with fibronectin or an anti-integrin antibody was restrained with an optical trap on fibroblasts to mimic extracellular attachment sites of different resistance. Cells precisely sense the restraining force on fibronectin beads and respond by a localized, proportional strengthening of the cytoskeleton linkages, allowing stronger force to be exerted on the integrins. This strengthening was absent or transient with antibody beads, but restored with soluble fibronectin. Hence, ligand binding site occupancy was required. Finally, phenylarsine oxide inhibited strengthening of cytoskeletal linkages, indicating a role for dephosphorylation. Thus, the strength of integrin-cytoskeleton linkages is dependent on matrix rigidity and on its biochemical composition. Matrix rigidity may, therefore, serve as a guidance cue in a process of mechanotaxis.
为了向前移动，迁移细胞必须通过与细胞外基质分子结合的表面受体产生牵引力，这些分子与刚性结构相连。我们研究了细胞是否会对锚定基质的硬度进行采样并做出反应。用光学镊子限制涂有纤连蛋白或抗整合素抗体的珠子在成纤维细胞上的移动，以模拟不同阻力的细胞外附着位点。细胞能精确感知纤连蛋白包被珠子上的阻力，并通过局部、成比例地加强细胞骨架连接做出反应，从而能够对整合素施加更大的力。抗体包被的珠子则不会出现这种增强现象，或者增强是短暂的，但加入可溶性纤连蛋白后这种增强得以恢复。因此，需要配体结合位点被占据。最后，苯砷氧化物抑制了细胞骨架连接的增强，表明去磷酸化发挥了作用。因此，整合素与细胞骨架连接的强度取决于基质硬度及其生化组成。因此，基质硬度可能在机械性趋化过程中作为一种引导信号。
