Fibrin binds to collagen and provides a bridge for αVβ3 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. 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.
*Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, BMC Box 582, SE-751 23 Uppsala, Sweden.
Vahid
V
Reyhani
*Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, BMC Box 582, SE-751 23 Uppsala, Sweden.
Pegah
P
Seddigh
†Department of Microbiology, BioCentrum, Swedish University of Agricultural Sciences, Box 7025, SE-750 07 Uppsala, Sweden.
Bengt
B
Guss
‡Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden.
Renata
R
Gustafsson
*Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, BMC Box 582, SE-751 23 Uppsala, Sweden.
Lars
L
Rask
Kristofer
K
Rubin
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism*; D005782:Gels; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D051379:Mice; D013917:Thrombin / Q000494:pharmacology
D024042:Collagen Type I; D005782:Gels; D039302:Integrin alphaVbeta3; D005337:Fibrin; D013917:Thrombin