Modulation of cell-fibronectin matrix interactions during tissue repair

Kim S. Midwood, Yong Mao, Henry C. Hsia, Leyla V. Valenick, Jean E. Schwarzbauer

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Environmental signals from the extracellular matrix (ECM) are transmitted by cell surface receptors that connect to the actin cytoskeleton and to multiple intracellular signaling pathways. To dissect how the ECM regulates cell functions, we are using a three-dimensional (3D) fibrin-fibronectin matrix, resembling the wound provisional matrix. Fibroblasts adhere to fibronectin in this matrix via concomitant engagement of α5β1 integrin receptors and syndecan-4, a transmembrane proteoglycan. An adhesive phenotype is developed with actin stress fibers and activation of focal adhesion kinase (FAK) and Rho GTPase. Lack of syndecan-4 engagement, as occurs in the presence of the ECM protein tenascin-C, promotes a motile phenotype; FAK and Rho signaling are downregulated and filopodia are extended. Fibronectin matrices have distinct effects on two other receptors: α4β1 and αvβ3 integrins. Although α4β1 does not naturally support strong cell interactions with a fibrin-fibronectin matrix, binding is dramatically enhanced by proteolytic cleavage of fibronectin. Conversely, activity of αvβ3 is stimulated by multimeric fibronectin fibrils showing that the organization of fibronectin differentially affects integrin functions. Thus, deposition of additional ECM components, expression of co-receptors for ECM, cleavage of adhesive proteins, and the architecture of the ECM microenvironment are different mechanisms for modulating cell responses to fibronectin matrix.

Original languageEnglish (US)
Pages (from-to)73-78
Number of pages6
JournalJournal of Investigative Dermatology Symposium Proceedings
Volume11
Issue number1
DOIs
StatePublished - Sep 1 2006

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Molecular Biology
  • Dermatology
  • Cell Biology

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