Fibronectin fibrillogenesis regulates three-dimensional neovessel formation

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

Research output: Contribution to journalArticlepeer-review

149 Scopus citations


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 languageEnglish (US)
Pages (from-to)1231-1243
Number of pages13
JournalGenes and Development
Issue number9
StatePublished - May 1 2008


  • Actomyosin
  • Angiogenesis
  • Endothelial cells
  • Extracellular matrix
  • Fibronectin

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


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