Université de Paris, CNRS, Institut Jacques Monod (IJM), Paris, France.
Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.
Nat Mater. 2021 Aug;20(8):1156-1166. doi: 10.1038/s41563-021-00919-2. Epub 2021 Feb 18.
Actomyosin machinery endows cells with contractility at a single-cell level. However, within a monolayer, cells can be contractile or extensile based on the direction of pushing or pulling forces exerted by their neighbours or on the substrate. It has been shown that a monolayer of fibroblasts behaves as a contractile system while epithelial or neural progentior monolayers behave as an extensile system. Through a combination of cell culture experiments and in silico modelling, we reveal the mechanism behind this switch in extensile to contractile as the weakening of intercellular contacts. This switch promotes the build-up of tension at the cell-substrate interface through an increase in actin stress fibres and traction forces. This is accompanied by mechanotransductive changes in vinculin and YAP activation. We further show that contractile and extensile differences in cell activity sort cells in mixtures, uncovering a generic mechanism for pattern formation during cell competition, and morphogenesis.
肌动球蛋白机械赋予细胞在单细胞水平的收缩性。然而,在单层中,细胞可以是收缩性的或伸展性的,这取决于其相邻细胞或基底施加的推或拉力的方向。已经表明,成纤维细胞的单层表现为收缩系统,而上皮或神经前体细胞的单层表现为伸展系统。通过细胞培养实验和计算机建模的组合,我们揭示了这种从伸展到收缩的转变的机制,即细胞间连接的减弱。这种转变通过增加肌动蛋白应力纤维和牵引力促进了细胞-基底界面张力的积累。这伴随着黏着斑蛋白和 YAP 激活的力学转导变化。我们进一步表明,细胞活性的收缩性和伸展性差异会在混合物中对细胞进行分类,揭示了细胞竞争和形态发生过程中模式形成的通用机制。