QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Research Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Zhou, X. Articles by Weiss, S. J. PubMed PubMed Citation Articles by Zhou, X. Articles by Weiss, S. J. Social Bookmarking                   What's this?

Fibronectin fibrillogenesis regulates three-dimensional neovessel formation

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

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.

[Keywords: Actomyosin; angiogenesis; endothelial cells; extracellular matrix; fibronectin]]

Received December 14, 2007; revised version accepted March 10, 2008.

⁷ Corresponding author.

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.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?