Matrix dynamics influence how individual cells develop into complex multicellular tissues. Here, we develop hydrogels with identical polymer components but different crosslinking capacities to enable the investigation of mechanisms underlying vascular morphogenesis. We show that dynamic (D) hydrogels increase the contractility of human endothelial colony-forming cells (hECFCs), promote the clustering of integrin β1, and promote the recruitment of vinculin, leading to the activation of focal adhesion kinase (FAK) and metalloproteinase expression. This leads to the robust assembly of vasculature and the deposition of new basement membrane. We also show that non-dynamic (N) hydrogels do not promote FAK signaling and that stiff D- and N-hydrogels are constrained for vascular morphogenesis. Furthermore, D-hydrogels promote hECFC microvessel formation and angiogenesis in vivo. Our results indicate that cell contractility mediates integrin signaling via inside-out signaling and emphasizes the importance of matrix dynamics in vascular tissue formation, thus informing future studies of vascularization and tissue engineering applications.

基质动力学影响单个细胞如何发育成复杂的多细胞组织。在这里，我们开发了具有相同聚合物成分但不同交联能力的水凝胶，以便能够研究血管形态发生的机制。我们发现动态（D）水凝胶可增加人内皮集落形成细胞（hECFC）的收缩性，促进整合素β1的聚集，并促进纽蛋白的募集，从而激活粘着斑激酶（FAK）和金属蛋白酶的表达。这导致脉管系统的稳健组装和新基底膜的沉积。我们还表明，非动态 (N) 水凝胶不会促进 FAK 信号传导，并且僵硬的 D-和 N-水凝胶对于血管形态发生受到限制。此外，D-水凝胶在体内促进 hECFC 微血管形成和血管生成。我们的结果表明，细胞收缩性通过由内而外的信号传导介导整合素信号传导，并强调基质动力学在血管组织形成中的重要性，从而为未来的血管化和组织工程应用研究提供信息。