Protrusive Activity Guides Changes in Cell-Cell Tension during Epithelial Cell Scattering
Protrusive Activity Guides Changes in Cell-Cell Tension during Epithelial Cell Scattering
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DOI：
10.1016/j.bpj.2014.06.028
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发表时间：
2014-08-05
影响因子：
3.4
通讯作者：
Gardel, Margaret L.
中科院分区：
文献类型：
--
作者：
Maruthamuthu, Venkat;Gardel, Margaret L.
了解上皮细胞如何调节细胞-基质和细胞-细胞粘附对于理解形态发生中的关键事件以及诸如转移的病理事件至关重要。在上皮细胞分散期间，上皮细胞岛破裂其细胞-细胞接触，并在生长因子刺激的数小时内作为细胞外基质（ECM）上的单个细胞迁移离开，即使粘附分子如E-钙粘蛋白存在于细胞-细胞接触处。如何调节细胞间接触的稳定性以影响这种形态学转变仍不清楚。在这里，我们报告说，在ECM的情况下，E-钙粘蛋白粘附继续维持实质性的细胞产生的力量后，肝细胞生长因子（HGF）的刺激，与不减弱的粘附强度一致。在存在局灶性粘连的情况下，阻止细胞在游离岛边缘扩散和移动的限制也防止了HGF介导的接触破裂。为了探索细胞运动和细胞-细胞接触破裂的作用，我们研究了细胞对分散过程中发生的生物物理变化。我们发现，细胞运动的方向与细胞间接触的平均细胞间力的变化，以及细胞间接触破裂的初始方向相关。我们的研究结果表明，在散射过程中，细胞位移和力的重新分配在引导细胞-细胞接触破裂中起着重要的作用。
Knowing how epithelial cells regulate cell-matrix and cell-cell adhesions is essential to understand key events in morphogenesis,as well as pathological events such as metastasis. During epithelial cell scattering, epithelial cell islands rupture their cell-cell contacts and migrate away as single cells on the extracellular matrix (ECM) within hours of growth factor stimulation, even as adhesion molecules such as E-cadherin are present at the cell-cell contact. How the stability of cell-cell contacts is modulated to effect such morphological transitions is still unclear. Here, we report that in the absence of ECM, E-cadherin adhesions continue to sustain substantial cell-generated forces upon hepatocyte growth factor (HGF) stimulation, consistent with undiminished adhesion strength. In the presence of focal adhesions, constraints that preclude the spreading and movement of cells at free island edges also prevent HGF-mediated contact rupture. To explore the role of cell motion and cell-cell contact rupture, we examine the biophysical changes that occur during the scattering of cell pairs. We show that the direction of cell movement with respect to the cell-cell contact is correlated with changes in the average intercellular force as well as the initial direction of cell-cell contact rupture. Our results suggest an important role for protrusive activity resulting in cell displacement and force redistribution in guiding cell-cell contact rupture during scattering.