title: Stretching fibronectin fibres disrupts binding of bacterial adhesins by physically destroying an epitope.
abstract: 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.
authors.affiliation: Department of Materials, ETH Zurich, Zürich CH-8093, Switzerland.
authors.forename: Mamta
authors.initials: M
authors.lastname: Chabria
authors.forename: Samuel
authors.initials: S
authors.lastname: Hertig
authors.forename: Michael L
authors.initials: ML
authors.lastname: Smith
authors.forename: Viola
authors.initials: V
authors.lastname: Vogel
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D005353:Fibronectins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006860:Hydrogen Bonding; D018613:Microscopy, Confocal; D011485:Protein Binding; D013211:Staphylococcus aureus / Q000378:metabolism; D013291:Streptococcus / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D000939:Epitopes; D005353:Fibronectins