Cell Stem Cell
Volume 27, Issue 5, 5 November 2020, Pages 798-812.e6
Journal home page for Cell Stem Cell

Article
Hydrogel Network Dynamics Regulate Vascular Morphogenesis

https://doi.org/10.1016/j.stem.2020.08.005Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Development of dynamic hydrogels to study matrix dynamics role in vascular assembly

  • Dynamic hydrogels promote cell contractility-mediated integrin clustering

  • Non-dynamic hydrogels prevent integrin clustering, subsequently inhibiting morphogenesis

  • Dynamic hydrogels promote the formation of microvessels and angiogenesis in vivo

Summary

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.

Keywords

stress-relaxation
vasculogenesis
integrin clustering
cell contractility

Cited by (0)

5

These authors contributed equally

6

Present address: The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, P.R. China

7

Lead Contact