Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
J Cell Biol. 2012 Oct 29;199(3):545-63. doi: 10.1083/jcb.201207148. Epub 2012 Oct 22.
The mechanical microenvironment is known to influence single-cell migration; however, the extent to which mechanical cues affect collective migration of adherent cells is not well understood. We measured the effects of varying substrate compliance on individual cell migratory properties in an epithelial wound-healing assay. Increasing substrate stiffness increased collective cell migration speed, persistence, and directionality as well as the coordination of cell movements. Dynamic analysis revealed that wounding initiated a wave of motion coordination from the wound edge into the sheet. This was accompanied by a front-to-back gradient of myosin-II activation and establishment of cell polarity. The propagation was faster and farther reaching on stiff substrates, indicating that substrate stiffness affects the transmission of directional cues. Manipulation of myosin-II activity and cadherin-catenin complexes revealed that this transmission is mediated by coupling of contractile forces between neighboring cells. Thus, our findings suggest that the mechanical environment integrates in a feedback with cell contractility and cell-cell adhesion to regulate collective migration.
机械微环境已知会影响单细胞迁移；然而，机械线索对贴壁细胞集体迁移的影响程度还不是很清楚。我们在一个上皮细胞伤口愈合实验中测量了不同基底顺应性对单个细胞迁移特性的影响。增加基底硬度会增加细胞的集体迁移速度、持续性和方向性，以及细胞运动的协调性。动态分析显示，伤口会从伤口边缘向薄片引发一波运动协调。这伴随着肌球蛋白-II 激活和细胞极性的建立的前后梯度。在硬基底上，传播速度更快，传播范围更广，这表明基底硬度会影响方向线索的传递。肌球蛋白-II 活性和钙粘蛋白-连环蛋白复合物的操纵表明，这种传递是通过相邻细胞之间的收缩力耦合来介导的。因此，我们的研究结果表明，机械环境与细胞收缩力和细胞-细胞黏附一起整合在反馈中，以调节集体迁移。
