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Regulation of Matrix Assembly through Rigidity-dependent Fibronectin Conformational Changes

Author(s): Carraher, Cara L; Schwarzbauer, Jean E

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Abstract: Cells sense and respond to the mechanical properties of their microenvironment. We investigated whether these properties affect the ability of cells to assemble a fibrillar fibronectin (FN) matrix. Analysis of matrix assembled by cells grown on FN-coated polyacrylamide gels of varying stiffnesses showed that rigid substrates stimulate FN matrix assembly and activation of focal adhesion kinase (FAK) compared with the level of assembly and FAK signaling on softer substrates. Stimulating integrins with Mn2 treatment increased FN assembly on softer gels, suggesting that integrin binding is deficient on soft substrates. Guanidine hydrochloride-induced extension of the substrate-bound FN rescued assembly on soft substrates to a degree similar to that of Mn2 treatment and increased activation of FAK along with the initiation of assembly at FN matrix assembly sites. In contrast, increasing actin-mediated cell contractility did not rescue FN matrix assembly on soft substrates. Thus, rigidity-dependent FN matrix assembly is determined by extracellular events, namely the engagement of FN by cells and the induction of FN conformational changes. Extensibility of FN in response to substrate stiffness may serve as a mechanosensing mechanism whereby cells use pericellular FN to probe the stiffness of their environment.
Publication Date: 24-May-2013
Electronic Publication Date: 15-Apr-2013
Citation: Carraher, Cara L, Schwarzbauer, Jean E. (2013). Regulation of Matrix Assembly through Rigidity-dependent Fibronectin Conformational Changes. Journal of Biological Chemistry, 288 (21), 14805 - 14814. doi:10.1074/jbc.M112.435271
DOI: doi:10.1074/jbc.M112.435271
ISSN: 0021-9258
EISSN: 1083-351X
Pages: 14805 - 14814
Type of Material: Journal Article
Journal/Proceeding Title: Journal of Biological Chemistry
Version: Final published version. Article is made available in OAR by the publisher's permission or policy.

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