Integrin-mediated cell adhesion to type I collagen fibrils

In the integrin family, the collagen receptors form a structurally and functionally distinct subgroup. Two members of this subgroup, α₁β₁ and α₂β₁ integrins, are known to bind to monomeric form of type I collagen. However, in tissues type I collagen monomers are organized into large fibrils immediately after they are released from cells. Here, we studied collagen fibril recognition by integrins. By an immunoelectron microscopy method we showed that integrin α₂I domain is able to bind to classical D-banded type I collagen fibrils. However, according to the solid phase binding assay, the collagen fibril formation appeared to reduce integrin α₁I and α₂I domain avidity to collagen and to lower the number of putative αI domain binding sites on it. Respectively, cellular α₁β₁ integrin was able to mediate cell spreading significantly better on monomeric than on fibrillar type I collagen matrix, whereas α₂β₁ integrin appeared still to facilitate both cell spreading on fibrillar type I collagen matrix and also the contraction of fibrillar type I collagen gel. Additionally, α₂β₁ integrin promoted the integrin-mediated formation of long cellular projections typically induced by fibrillar collagen. Thus, these findings suggest that α₂β₁ integrin is a functional cellular receptor for type I collagen fibrils, whereas α₁β₁ integrin may only effectively bind type I collagen monomers. Furthermore, when the effect of soluble αI domains on type I collagen fibril formation was tested in vitro, the observations suggest that integrin type collagen receptors might guide or even promote pericellular collagen fibrillogenesis.