The β1-null fibroblastic cell line GD25 and its derivatives were studied to gain an understanding of the roles of β1 and β3 integrins in the initial (1-hour) contraction of collagen gels. Stable transfectants


Cells experience physical force directed toward them and exert force upon their surroundings. The cytoskeleton of the cell provides the tensional force to counteract the mechanical load of the extracellular matrix (ECM) on mesenchymal cells or sheer stress exerted on endothelial cells (Ingber, 1991; Davies, 1995; Kolodney and Wysolmerski, 1992). Perturbations of this force balance result in alterations in cell behavior. Threedimensional collagen gels provide a model to study tensional forces between cells and ECM (Bell et al., 1979; Elsdale and Bard 1972; Brown et al., 1996; Grinnell, 1994). The force balance can be altered by releasing the matrix gel from its attachment to the substratum, thus abolishing tensional forces generated by attachment. This change in mechanical environment provokes cellular responses leading to rearrangement of cytoskeleton and modified biosynthesis (Mochitate et al., 1991; Lambert et al., 1998; Tomasek et al., 1982; Nakagawa et al., 1989; Clark et al., 1995) and has been suggested to recapitulate events occurring during embryogenesis, wound healing and cell migration (Stopak and Harris, 1982; Tomasek et al., 1982). Among the genes exhibiting altered expression by fibroblasts cultured in attached versus non-attached collagen gels are those for α2 integrin subunit (Klein et al., 1991; Xu et al., 1998), matrix metalloproteinase-1 (Langholz et al., 1995), tenascin-C (Chiquet-Ehrismann et al., 1994), type 1 collagen (Eckes et al., 1993), and c-fos (Rosenfeldt et al., 1998). Fibronectin assembly and stress fiber formation are also altered by fibroblasts grown in collagen gels under different tensional environments (Halliday and Tomasek, 1995). Transduction of mechanical signal from the ECM to the cell requires a continuum of structural elements and is thought to be mediated by integrins (Ingber, 1991; Shyy and Chien, 1997; Maniotis et al., 1997). Several studies have demonstrated a role for β1 integrins, in particular α1β1 and α2β1, in mediating, collagen gel contraction by fibroblasts and osteoblastic cells (Gullberg et al., 1990; Carver et al., 1995; Langholz et al., 1995; Werb et al., 1990; Shiro et al., 1991; Riikonen et al., 1995; Grinnell, 1994; Clark et al., 1989). Langholz et al. (1995), using monoclonal antibodies (mAb) to α1, α2, α3, β1, α1β1, and α2β1 on human fibroblasts, found the greatest inhibition of contraction with mAb to α2β1, although complete inhibition could not be demonstrated. This result suggests that α2β1 is the major, but not the only, mediator of contraction. Serum or a purified agonist is required for collagen gel contraction (Tomasek et al., 1992; Guidry and Grinnell, 1985). Various cells have enhanced collagen gel contraction upon the addition of platelet derived growth factor (PDGF), insulin-like growth factor, basic fibroblast growth factor, transforming 2375 Journal of Cell Science 113, 2375-2383 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 JCS1082


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