Hydrogel Network Dynamics Regulate Vascular Morphogenesis
Hydrogel Network Dynamics Regulate Vascular Morphogenesis
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DOI：
10.2139/ssrn.3553544
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发表时间：
2020-03
期刊：
影响因子：
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通讯作者：
Zhao Wei;Rahel Schnellmann;S. Gerecht
中科院分区：
文献类型：
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作者：
Zhao Wei;Rahel Schnellmann;S. Gerecht
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，我们开发具有相同聚合物组分但不同交联性的水凝胶，以使研究血管形态发生的机制成为可能。我们发现动态(D)水凝胶增加了人内皮细胞集落形成细胞(HECFC)的收缩能力，促进了整合素β1的聚集，并促进了纽蛋白的募集，导致粘着斑激酶的激活和金属蛋白酶的表达。这导致血管系统的强大组装和新的基底膜的沉积。我们还表明，非动态(N)水凝胶不促进FAK信号转导，而刚性D-和N-水凝胶对血管形态发生有限制作用。此外，D-水凝胶在体内可促进hECFC微血管形成和血管生成。我们的结果表明，细胞收缩通过自内向外信号传递整合素信号，并强调了基质动力学在血管组织形成中的重要性，从而为未来血管形成和组织工程应用的研究提供了信息。
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.