Extracellular matrix rigidity causes strengthening of integrin-cytoskeleton linkages
Extracellular matrix rigidity causes strengthening of integrin-cytoskeleton linkages
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DOI：
10.1016/s0092-8674(00)81856-5
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发表时间：
1997-01-10
期刊：
影响因子：
64.5
通讯作者：
Sheetz, MP
中科院分区：
文献类型：
--
作者：
Choquet, D;Felsenfeld, DP;Sheetz, MP
为了向前移动，迁移的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，这些受体与刚性结构相连。我们研究了细胞是否会对锚定基质的刚性进行检测并作出反应。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珠子上的限制力，并通过局部、成比例地增强细胞骨架连接来作出反应，从而能对整合素施加更强的力。这种增强作用在抗体珠子上不存在或只是短暂的，但加入可溶性纤连蛋白后会恢复。因此，配体结合位点的占据是必需的。最后，苯胂氧化物抑制了细胞骨架连接的增强，表明去磷酸化起作用。因此，整合素 - 细胞骨架连接的强度取决于基质的刚性及其生化组成。基质刚性可能因此在趋机械性过程中作为一种导向信号。
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.