Endothelial tube formation on a reconstituted basement membrane (Matrigel) is a well-established in vitro model for studying the processes of angiogenesis and vasculogenesis. However, to date, the organizing principles that underlie the morphogenesis of this network and that shape the initial process of cells’ finding one another remain elusive. Here, we identify a mechanism that allows cells to form networks by mechanically reorganizing and stiffening their extracellular matrix, independent of chemical guidance cues. Interestingly, we find that this cellular self-organization strongly depends on the connectivity, plasticity, and topology of the surrounding matrix; cell contractility; and cell density. Cells rearrange the matrix and form bridges of matrix material that are stiffer than their surroundings, thus creating a durotactic track for the initiation of cell protrusions and cell-cell contacts. This contractility-based communication via strain stiffening and matrix rearrangement might be a general organizing principle during tissue development or regeneration.

重组基底膜（Matrigel）上的内皮管形成是公认的体外方法用于研究血管生成和血管生成过程的模型。然而，迄今为止，构成该网络形态发生基础并影响细胞相互寻找的初始过程的组织原理仍然难以捉摸。在这里，我们确定了一种机制，该机制允许细胞通过机械重组和强化其细胞外基质而独立于化学指导，从而形成网络。有趣的是，我们发现这种细胞的自组织在很大程度上取决于周围基质的连通性，可塑性和拓扑。细胞收缩性 和细胞密度。细胞重新排列基质，并形成比其周围环境更硬的基质材料的桥，从而为细胞突起和细胞-细胞接触的起始创建了一条多向轨道。