Interactions of human skin fibroblasts with monomeric or fibrillar collagens induce different organization of the cytoskeleton.
Fibrillar collagens represent the most abundant extracellular matrix components surrounding fibroblasts. Although there is a large heterogeneity in the collagen composition and in the physiological functions of different tissues, interactions between cells and native collagens monomers are mediated by only two integrins, the alpha1beta1 and alpha2beta1 integrins. In tissue, fibroblasts are exposed to collagen polymers, supramolecular assemblies which might play a role on the availability of the cell-binding sites at the surface of the fibrils. We have addressed this issue by investigating the patterns of adhesion structures in normal human skin fibroblasts exposed to collagen monomers or polymers. Our results showed that cell morphology, cell adhesion pattern, actin organization, and distribution of integrin subunits, talin, vinculin, and phosphotyrosine-containing proteins are dependent on the supramolecular organization of the collagens. In particular, compared to monomers, collagen polymers induced a looser organization of the actin network and a linear clustering of integrins, talin, vinculin, and phosphotyrosine-containing proteins. These results emphasize the role of the physical state of collagen on cellular interactions and underline the role of the extracellular matrix in the phenotypic modulation of fibroblasts. Furthermore, our studies suggest the existence of a local heterogeneity in the biological activity of collagen fibrils.
Mercier
I
I
CNRS UPR 412, Institut de Biologie et Chimie des Protéines, Lyon, France.
Lechaire
J P
JP
Desmouliere
A
A
Gaill
F
F
Aumailley
M
M
D000199:Actins / Q000032:analysis; D002478:Cells, Cultured / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D003094:Collagen / Q000494:pharmacology*; D003599:Cytoskeleton / Q000737:chemistry / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D016023:Integrins / Q000032:analysis; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D010507:Periodicity; D019000:Phosphotyrosine / Q000032:analysis; D012867:Skin / Q000166:cytology*; D016608:Talin / Q000032:analysis; D016596:Vinculin / Q000032:analysis
D000199:Actins; D016023:Integrins; D016608:Talin; D016596:Vinculin; D019000:Phosphotyrosine; D003094:Collagen