Department of Engineering Science and Mechanics, Pennsylvania State University, University Park, PA 16802.
Department of Biomedical Engineering, Pennsylvania State University, University Park, PA 16802.
Proc Natl Acad Sci U S A. 2020 Dec 29;117(52):33263-33271. doi: 10.1073/pnas.2010960117. Epub 2020 Dec 14.
Gap closure to eliminate physical discontinuities and restore tissue integrity is a fundamental process in normal development and repair of damaged tissues and organs. Here, we demonstrate a nonadhesive gap closure model in which collective cell migration, large-scale actin-network fusion, and purse-string contraction orchestrate to restore the gap. Proliferative pressure drives migrating cells to attach onto the gap front at which a pluricellular actin ring is already assembled. An actin-ring segment switching process then occurs by fusion of actin fibers from the newly attached cells into the actin cable and defusion from the previously lined cells, thereby narrowing the gap. Such actin-cable segment switching occurs favorably at high curvature edges of the gap, yielding size-dependent gap closure. Cellular force microscopies evidence that a persistent rise in the radial component of inward traction force signifies successful actin-cable segment switching. A kinetic model that integrates cell proliferation, actin fiber fusion, and purse-string contraction is formulated to quantitatively account for the gap-closure dynamics. Our data reveal a previously unexplored mechanism in which cells exploit multifaceted strategies in a highly cooperative manner to close nonadhesive gaps.
间隙闭合是一种基本过程，它可以消除物理不连续性，恢复组织完整性，这在正常发育和受损组织与器官修复中都发挥着重要作用。在这里，我们展示了一种无黏附性的间隙闭合模型，其中细胞的集体迁移、大规模肌动蛋白网络融合和束带收缩共同作用以恢复间隙。增殖压力驱使迁移细胞附着在间隙前缘，此时已经组装了一个多细胞肌动蛋白环。然后，通过将新附着细胞中的肌动蛋白纤维融合到肌动蛋白电缆中，并从先前排列的细胞中解聚，发生肌动蛋白电缆段切换过程，从而缩小间隙。这种肌动蛋白电缆段切换有利于间隙的高曲率边缘，从而产生与尺寸相关的间隙闭合。细胞力显微镜证据表明，向内牵引力的径向分量持续上升表明肌动蛋白电缆段切换成功。我们提出了一个整合细胞增殖、肌动蛋白纤维融合和束带收缩的动力学模型，以定量解释间隙闭合动力学。我们的数据揭示了一种以前未被探索的机制，其中细胞以高度协作的方式利用多方面的策略来闭合无黏附性间隙。
