Hydrogel Network Dynamics Regulate Vascular Morphogenesis

Zhao Wei, Rahel Schnellmann, Hawley C. Pruitt, Sharon Gerecht

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)798-812.e6
JournalCell stem cell
Volume27
Issue number5
DOIs
StatePublished - Nov 5 2020

Keywords

  • cell contractility
  • integrin clustering
  • stress-relaxation
  • vasculogenesis

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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