title: Integrin-mediated cell adhesion to type I collagen fibrils.
abstract: In the integrin family, the collagen receptors form a structurally and functionally distinct subgroup. Two members of this subgroup, alpha(1)beta(1) and alpha(2)beta(1) 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 alpha(2)I 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 alpha(1)I and alpha(2)I domain avidity to collagen and to lower the number of putative alphaI domain binding sites on it. Respectively, cellular alpha(1)beta(1) integrin was able to mediate cell spreading significantly better on monomeric than on fibrillar type I collagen matrix, whereas alpha(2)beta(1) 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, alpha(2)beta(1) integrin promoted the integrin-mediated formation of long cellular projections typically induced by fibrillar collagen. Thus, these findings suggest that alpha(2)beta(1) integrin is a functional cellular receptor for type I collagen fibrils, whereas alpha(1)beta(1) integrin may only effectively bind type I collagen monomers. Furthermore, when the effect of soluble alphaI 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.
authors.affiliation: Department of Biological and Environmental Science, University of Jyväskylä, Jyväskylä FI-40014, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Jokinen
authors.forename: Elina
authors.initials: E
authors.lastname: Dadu
authors.forename: Petri
authors.initials: P
authors.lastname: Nykvist
authors.forename: Jarmo
authors.initials: J
authors.lastname: Käpylä
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: White
authors.forename: Johanna
authors.initials: J
authors.lastname: Ivaska
authors.forename: Piia
authors.initials: P
authors.lastname: Vehviläinen
authors.forename: Hilkka
authors.initials: H
authors.lastname: Reunanen
authors.forename: Hannu
authors.initials: H
authors.lastname: Larjava
authors.forename: Lari
authors.initials: L
authors.lastname: Häkkinen
authors.forename: Jyrki
authors.initials: J
authors.lastname: Heino
mesh_terms: D000818:Animals; D016466:CHO Cells; D002417:Cattle; D002448:Cell Adhesion / Q000502:physiology*; D024042:Collagen Type I / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D006224:Cricetinae; D006801:Humans; D066298:In Vitro Techniques; D039222:Integrin alpha1beta1 / Q000378:metabolism; D038982:Integrin alpha2beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D039222:Integrin alpha1beta1; D038982:Integrin alpha2beta1; D016023:Integrins; D011993:Recombinant Fusion Proteins