caa a22 4500 528786466 20190713030957.0 cr unu---uuuuu 180924s2010 xx s 000 0 eng 10.3929/ethz-b-000159233 doi 10.1038/ncomms1135 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/159233 Stretching fibronectin fibres disrupts binding of bacterial adhesins by physically destroying an epitope [Elektronische Daten] [Mamta Chabria, Samuel Hertig, Michael L. Smith, Viola Vogel] Nat Commun Open access ethresearch Although soluble inhibitors are frequently used to block cell binding to the extracellular matrix (ECM), mechanical stretching of a protein fibre alone can physically destroy a cell-binding site. Here, we show using binding assays and steered molecular dynamics that mechanical tension along fibronectin (Fn) fibres causes a structural mismatch between Fn-binding proteins from Streptococcus dysgalactiae and Staphylococcus aureus. Both adhesins target a multimodular site on Fn that is switched to low affinity by stretching the intermodular distances on Fn. Heparin reduces binding but does not eliminate mechanosensitivity. These adhesins might thus preferentially bind to sites at which ECM fibres are cleaved, such as wounds or inflamed tissues. The mechanical switch described here operates differently from the catch bond mechanism that Escherichia coli uses to adhere to surfaces under fluid flow. Demonstrating the existence of a mechanosensitive cell-binding site provides a new perspective on how the mechanobiology of ECM might regulate bacterial and cell-binding events, virulence and the course of infection. Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported http://creativecommons.org/licenses/by-nc-nd/3.0 ethresearch Chabria Mamta joint author Hertig Samuel joint author Smith Michael L. joint author Vogel Viola joint author Nature Communications London : Nature Publishing Group 1, p. 135 2041-1723 http://hdl.handle.net/20.500.11850/159233 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/159233 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Chabria Mamta joint author ETHRESEARCH 700 1- Hertig Samuel joint author ETHRESEARCH 700 1- Smith Michael L. joint author ETHRESEARCH 700 1- Vogel Viola joint author ETHRESEARCH 773 0- Nature Communications London : Nature Publishing Group 1, p. 135 2041-1723 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access