Fibrin binds to collagen and provides a bridge for αVβ3 integrin-dependent contraction of collagen gels.
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Reyhani V, Seddigh P, Guss B, Gustafsson R, Rask L, Rubin K
Biochem. J. 462 (1) 113-123 [2014-08-15; online 2014-05-21]
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 αVβ3 integrins. This allowed murine myoblast C2C12 cells to contract the collagenous composite gel via αVβ3 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 αVβ3 integrins to Col I fibres and thereby promotes cell-mediated contraction of collagenous tissue structures.
PubMed 24840544
DOI 10.1042/BJ20140201
Crossref 10.1042/BJ20140201
pii: BJ20140201
pmc: PMC4109839