Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain.
Aragon Institute of Engineering Research (I3A), University of Zaragoza, 50018 Zaragoza, Spain.
Science. 2016 Sep 9;353(6304):1157-61. doi: 10.1126/science.aaf7119.
The ability of cells to follow gradients of extracellular matrix stiffness-durotaxis-has been implicated in development, fibrosis, and cancer. Here, we found multicellular clusters that exhibited durotaxis even if isolated constituent cells did not. This emergent mode of directed collective cell migration applied to a variety of epithelial cell types, required the action of myosin motors, and originated from supracellular transmission of contractile physical forces. To explain the observed phenomenology, we developed a generalized clutch model in which local stick-slip dynamics of cell-matrix adhesions was integrated to the tissue level through cell-cell junctions. Collective durotaxis is far more efficient than single-cell durotaxis; it thus emerges as a robust mechanism to direct cell migration during development, wound healing, and collective cancer cell invasion.
细胞跟随细胞外基质硬度梯度(趋硬性)的能力与发育、纤维化和癌症有关。在这里,我们发现即使单个组成细胞没有趋硬性,多细胞簇也表现出趋硬性。这种定向的集体细胞迁移的新兴模式适用于多种上皮细胞类型,需要肌球蛋白马达的作用,并源自细胞间收缩物理力的超细胞传递。为了解释所观察到的现象,我们开发了一个广义的离合器模型,其中细胞-基质黏附的局部粘滑动力学通过细胞-细胞连接整合到组织水平。集体趋硬性比单细胞趋硬性效率高得多;因此,它成为指导发育、伤口愈合和集体癌细胞侵袭过程中细胞迁移的一种强大机制。