Graduate Program in Biophysics, Stanford University, Stanford, California; Department of Chemical Engineering, Stanford University, Stanford, California.
Department of Biology and Howard Hughes Medical Institute, University of Washington, Seattle, Washington.
Biophys J. 2022 Mar 15;121(6):1029-1037. doi: 10.1016/j.bpj.2022.02.006. Epub 2022 Feb 12.
Adhesion between animal cells and the underlying extracellular matrix is challenged during wounding, cell division, and a variety of pathological processes. How cells recover adhesion in the immediate aftermath of detachment from the extracellular matrix remains incompletely understood, due in part to technical limitations. Here, we used acute chemical and mechanical perturbations to examine how epithelial cells respond to partial delamination events. In both cases, we found that cells extended lamellipodia to establish readhesion within seconds of detachment. These lamellipodia were guided by sparse membrane tethers whose tips remained attached to their original points of adhesion, yielding lamellipodia that appear to be qualitatively distinct from those observed during cell migration. In vivo measurements in the context of a zebrafish wound assay showed a similar behavior, in which membrane tethers guided rapidly extending lamellipodia. In the case of mechanical wounding events, cells selectively extended tether-guided lamellipodia in the direction opposite of the pulling force, resulting in the rapid reestablishment of contact with the substrate. We suggest that membrane tether-guided lamellipodial respreading may represent a general mechanism to reestablish tissue integrity in the face of acute disruption.
动物细胞与基底细胞外基质之间的黏附在创伤、细胞分裂和各种病理过程中受到挑战。由于技术限制，细胞在从细胞外基质上脱离后的立即恢复黏附的机制仍不完全清楚。在这里，我们使用急性化学和机械扰动来研究上皮细胞如何响应部分去分化事件。在这两种情况下，我们发现细胞延伸了伪足以在脱离后的几秒钟内重新建立黏附。这些伪足由稀疏的膜连接物引导，其尖端仍附着在原始黏附点上，从而产生的伪足在质量上似乎与在细胞迁移过程中观察到的不同。在斑马鱼伤口模型的体内测量中，观察到了类似的行为，其中膜连接物引导快速延伸的伪足。在机械创伤事件中，细胞在与拉力相反的方向选择性地延伸了由连接物引导的伪足，从而迅速重新与基底接触。我们认为，膜连接物引导的伪足延伸可能代表了一种在急性破坏的情况下重新建立组织完整性的普遍机制。
