Galbraith Catherine G, Yamada Kenneth M, Sheetz Michael P
Duke University Medical Center, Durham, NC 27710, USA.
J Cell Biol. 2002 Nov 25;159(4):695-705. doi: 10.1083/jcb.200204153.
To adhere and migrate, cells must be capable of applying cytoskeletal force to the extracellular matrix (ECM) through integrin receptors. However, it is unclear if connections between integrins and the ECM are immediately capable of transducing cytoskeletal contraction into migration force, or whether engagement of force transmission requires maturation of the adhesion. Here, we show that initial integrin-ECM adhesions become capable of exerting migration force with the recruitment of vinculin, a marker for focal complexes, which are precursors of focal adhesions. We are able to induce the development of focal complexes by the application of mechanical force to fibronectin receptors from inside or outside the cell, and we are able to extend focal complex formation to vitronectin receptors by the removal of c-Src. These results indicate that cells use mechanical force as a signal to strengthen initial integrin-ECM adhesions into focal complexes and regulate the amount of migration force applied to individual adhesions at localized regions of the advancing lamella.
为了实现黏附与迁移,细胞必须能够通过整合素受体向细胞外基质(ECM)施加细胞骨架力。然而,整合素与细胞外基质之间的连接是否能够立即将细胞骨架收缩转化为迁移力,或者力传递的发生是否需要黏附的成熟,目前尚不清楚。在这里,我们表明,随着纽蛋白(一种粘着斑复合体的标志物,粘着斑复合体是粘着斑的前体)的募集,最初的整合素 - 细胞外基质黏附能够施加迁移力。我们能够通过从细胞内部或外部对纤连蛋白受体施加机械力来诱导粘着斑复合体的形成,并且通过去除c - Src,我们能够将粘着斑复合体的形成扩展到玻连蛋白受体。这些结果表明,细胞利用机械力作为信号,将最初的整合素 - 细胞外基质黏附强化为粘着斑复合体,并在前进的片层局部区域调节施加到单个黏附的迁移力的大小。