Fibronectin fibrillogenesis regulates three-dimensional neovessel formation (original) (raw)
- Xiaoming Zhou1,6,
- R. Grant Rowe1,6,
- Nobuaki Hiraoka1,
- Jerry P. George2,
- Denis Wirtz2,
- Deane F. Mosher3,
- Ismo Virtanen4,
- Michael A. Chernousov5, and
- Stephen J. Weiss1,7
- 1 The Division of Molecular Medicine and Genetics, Department of Internal Medicine, The Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 2 Department of Chemical and Biomolecular Engineering and Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland 21218, USA;
- 3 Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA;
- 4 Institute of Biomedicine/Anatomy, University of Helsinki, FIN-00014 Finland;
- 5 Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 17822, USA
- ↵6 These authors contributed equally to this work.
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.
Footnotes
↵7 Corresponding author.
↵7 E-MAIL SJWEISS{at}umich.edu; FAX (734) 764-1934.Supplemental material is available at http://www.genesdev.org.
Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1643308.
- Received December 14, 2007.
- Accepted March 10, 2008.
Copyright © 2008, Cold Spring Harbor Laboratory Press