Physical state of the extracellular matrix regulates the structure and molecular composition of cell-matrix adhesions

Ben Zion Katz, Eli Zamir, Alexander Bershadsky, Zvi Kam, Kenneth M. Yamada, Benjamin Geiger

Research output: Contribution to journalArticlepeer-review

Abstract

This study establishes that the physical state of the extracellular matrix can regulate integrin-mediated cytoskeletal assembly and tyrosine phosphorylation to generate two distinct types of cell-matrix adhesions. In primary fibroblasts, α51 integrin associates mainly with fibronectin fibrils and forms adhesions structurally distinct from focal contacts, independent of actomyosin-mediated cell contractility. These 'fibrillar adhesions' are enriched in tensin, but contain low levels of the typical focal contact components paxillin, vinculin, and tyrosine-phosphorylated proteins. However, when the fibronectin is covalently linked to the substrate, α51 integrin forms highly tyrosine-phosphorylated, 'classical' focal contacts containing high levels of paxillin and vinculin. These experiments indicate that the physical state of the matrix, not just its molecular composition, is a critical factor in defining cytoskeletal organization and phosphorylation at adhesion sites. We propose that molecular organization of adhesion sites is controlled by at least two mechanisms: 1) specific integrins associate with their ligands in transmembrane complexes with appropriate cytoplasmic anchor proteins (e.g., fibronectin-α51 integrin-tensin complexes), and 2) physical properties (e.g., rigidity) of the extracellular matrix regulate local tension at adhesion sites and activate local tyrosine phosphorylation, recruiting a variety of plaque molecules to these sites. These mechanisms generate structurally and functionally distinct types of matrix adhesions in fibroblasts.

Original languageEnglish
Pages (from-to)1047-1060
Number of pages14
JournalMolecular Biology of the Cell
Volume11
Issue number3
DOIs
StatePublished - Mar 2000
Externally publishedYes

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