Fibrin binds to collagen and provides a bridge for alpha V beta 3 integrin-dependent contraction of collagen gels

Abstract

The functional significance of fibrin deposits typically seen in inflammatory lesions, carcinomas and in healing wounds is not fully understood. In the present study, we demonstrate that fibrinogen/fibrin specifically bound to native Col I (collagen type I) and used the Col I fibre network as a base to provide a functional interface matrix that connects cells to the Col I fibres through alpha V beta 3 integrins. This allowed murine myoblast C2C12 cells to contract the collagenous composite gel via alpha V beta 3 integrin. We show that fibrinogen specifically bound to immobilized native Col I at the site known to bind matrix metalloproteinase-1, discoidin domain receptor-2 and fibronectin, and that binding had no effect on Col I fibrillation. A specific competitive inhibitor blocking the Col-I-binding site for fibrinogen abolished the organization of fibrin into discernable fibrils, as well as the C2C12-mediated contraction of Col I gels. Our data show that fibrin can function as a linkage protein between Col I fibres and cells, and suggest that fibrin at inflammatory sites indirectly connects alpha V beta 3 integrins to Col I fibres and thereby promotes cell-mediated contraction of collagenous tissue structures.

Keywords

collagen type I; fibrin; gel contraction; interface matrix; protein binding

Published in

Biochemical Journal
2014, volume: 462, pages: 113-123
Publisher: PORTLAND PRESS LTD

SLU Authors

• Guss, Bengt

  • Department of Molecular Sciences, Swedish University of Agricultural Sciences
    

Global goals (SDG)

SDG3 Good health and well-being

UKÄ Subject classification

Microbiology
Microbiology in the medical area

Publication identifier

• DOI: https://doi.org/10.1042/BJ20140201

Permanent link to this page (URI)

https://res.slu.se/id/publ/63313