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Fibronectin fibrillogenesis regulates three-dimensional neovessel formation

By Xiaoming Zhou, R. Grant Rowe, Nobuaki Hiraoka, Jerry P. George, Denis Wirtz, Deane F. Mosher, Ismo Virtanen, Michael A. Chernousov and Stephen J. Weiss


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

Topics: Research Paper
Publisher: Cold Spring Harbor Laboratory Press
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Provided by: PubMed Central
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