Abstract
During vasculogenesis and angiogenesis, endothelial cell responses to growth factors are modulated by the compositional and mechanical properties of a surrounding three-dimensional (3D) extracellular matrix (ECM) that is dominated by either cross-linked fibrin or type I collagen. While 3D-embedded endothelial cells establish adhesive interactions with surrounding ligands to optimally respond to soluble or matrix-bound agonists, the manner in which a randomly ordered ECM with diverse physico-mechanical properties is remodeled to support blood vessel formation has remained undefined. Herein, we demonstrate that endothelial cells initiate neovascularization by unfolding soluble fibronectin (Fn) and depositing a pericellular network of fibrils that serve to support cytoskeletal organization, actomyosin-dependent tension, and the viscoelastic properties of the embedded cells in a 3D-specific fashion. These results advance a new model wherein Fn polymerization serves as a structural scaffolding that displays adhesive ligands on a mechanically ideal substratum for promoting neovessel development.
Original language | English (US) |
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Pages (from-to) | 1231-1243 |
Number of pages | 13 |
Journal | Genes and Development |
Volume | 22 |
Issue number | 9 |
DOIs | |
State | Published - May 1 2008 |
Keywords
- Actomyosin
- Angiogenesis
- Endothelial cells
- Extracellular matrix
- Fibronectin
ASJC Scopus subject areas
- Genetics
- Developmental Biology