Fibroblast-mediated collagen gel contraction does not require fibronectin-alpha 5 beta 1 integrin interaction.
Fibroblasts cultured within free-floating collagen gels can bind to and reorganize the surrounding collagen fibrils into a more dense and compact arrangement. Collagen gel contraction provides an in vitro model for studying fibroblast-collagen interactions important in wound healing, fibrosis, scar contraction, and connective tissue morphogenesis. We have assessed the role of fibronectin and its interaction with the alpha 5 beta 1 "high affinity" fibronectin-specific integrin receptor in collagen gel contraction. A variety of agents, which specifically inhibit fibronectin-alpha 5 beta 1 interactions, were tested for their abilities to inhibit fibroblast-mediated collagen gel contraction. These included anti-alpha 5 beta 1 monoclonal antibodies, the synthetic peptide GRGDSP, the cell adhesive fragment of fibronectin, and an antibody against the cell adhesive region of fibronectin. None of these agents inhibited collagen gel contraction. Therefore, it is concluded that fibronectin-alpha 5 beta 1 interactions are not necessary for collagen gel contraction. However, collagen gel contraction is dependent on a member or members of the beta 1 subfamily of integrin matrix receptors. A polyclonal antiserum and a monoclonal antibody, both directed against the beta 1 subunit of integrin matrix receptors, inhibited the spreading of fibroblasts in the collagen gel and inhibited collagen gel contraction. This study demonstrates that fibroblast-mediated collagen gel contraction is independent of fibronectin-alpha 5 beta 1 interactions but dependent on an interaction of beta 1 integrin matrix receptors with collagen fibers.
Tomasek
J J
JJ
Department of Anatomical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Akiyama
S K
SK
D000818:Animals; D002417:Cattle; D003094:Collagen / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D005312:Fetal Blood; D005347:Fibroblasts / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology*; D005782:Gels; D006801:Humans
D005353:Fibronectins; D005782:Gels; D003094:Collagen