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Fibronectin fibrillogenesis regulates three-dimensional neovessel formation.

Research paper by Xiaoming X Zhou, R Grant RG Rowe, Nobuaki N Hiraoka, Jerry P JP George, Denis D Wirtz, Deane F DF Mosher, Ismo I Virtanen, Michael A MA Chernousov, Stephen J SJ Weiss

Indexed on: 03 May '08Published on: 03 May '08Published in: Genes & development



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.