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

The functional significance of fibrin deposits typically seen in inflammatory lesions, carcinomas and in healing wounds is not fully understood. We demonstrate that fibrinogen/fibrin specifically bound to native collagen type I (Col I) and used the Col I fiber network as a base to providing a functional interface matrix that connects cells to the Col I fibers 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 fibers and cells and suggest that fibrin at inflammatory sites indirectly connects αVβ3 integrins to Col I fibers and thereby promotes cell-mediated contraction of collagenous tissue structures.
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Cell Source Type: research