School of Mechanical Engineering, Tel Aviv University, Tel Aviv 6997801, Israel.
Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv 6997801, Israel.
Mol Biol Cell. 2020 Jul 1;31(14):1474-1485. doi: 10.1091/mbc.E20-01-0079. Epub 2020 May 6.
When seeded in fibrous gels, pairs of cells or cell aggregates can induce bands of deformed gel, extending to surprisingly long distances in the intercellular medium. The formation of bands has been previously shown and studied in collagen systems. In this study, we strive to further our understanding of this fundamental mechanical mechanism in fibrin, a key element in wound healing and angiogenesis processes. We embedded fibroblast cells in 3D fibrin gels, and monitored band formation by real-time confocal microscopy. Quantitative dynamic analysis of band formation revealed a gradual increase in fiber density and alignment between pairs of cells. Such intercellular bands extended into a large-scale network of mechanically connected cells, in which the connected cells exhibited a more spread morphology than the isolated cells. Moreover, computational modeling demonstrated that the direction of cell-induced force triggering band formation can be applied in a wide range of angles relative to a neighboring cell. Our findings indicate that long-range mechanical coupling between cells is an important mechanism in regulating multicellular processes in reconstituted fibrin gels. As such, it should motivate exploration of this mechanism in studies in vivo, in wound healing or angiogenesis, in which fibrin is contracted by fibroblast cells.
当细胞对或细胞聚集体在纤维凝胶中播种时，它们可以诱导变形凝胶带的形成，在细胞间介质中延伸到惊人的远距离。这种凝胶带的形成以前在胶原蛋白系统中已经被展示和研究过。在这项研究中，我们努力进一步理解纤维蛋白中的这种基本机械机制，纤维蛋白是伤口愈合和血管生成过程中的关键元素。我们将成纤维细胞嵌入到 3D 纤维蛋白凝胶中，并通过实时共聚焦显微镜监测带的形成。对带形成的定量动态分析显示，细胞对之间的纤维密度和排列逐渐增加。这种细胞间的带延伸到一个由机械连接的细胞组成的大规模网络中，在这个网络中，连接的细胞比孤立的细胞具有更伸展的形态。此外，计算模型表明，触发带形成的细胞诱导力的方向可以相对于相邻细胞在很宽的角度范围内施加。我们的研究结果表明，细胞之间的长程机械耦合是调节纤维蛋白凝胶中细胞间多细胞过程的重要机制。因此，它应该激励在体内研究中探索这种机制，包括在伤口愈合或血管生成中，纤维蛋白被成纤维细胞收缩的情况。
