title: Rigidity sensing and adaptation through regulation of integrin types.
abstract: Tissue rigidity regulates processes in development, cancer and wound healing. However, how cells detect rigidity, and thereby modulate their behaviour, remains unknown. Here, we show that sensing and adaptation to matrix rigidity in breast myoepithelial cells is determined by the bond dynamics of different integrin types. Cell binding to fibronectin through either α5β1 integrins (constitutively expressed) or αvβ6 integrins (selectively expressed in cancer and development) adapts force generation, actin flow and integrin recruitment to rigidities associated with healthy or malignant tissue, respectively. In vitro experiments and theoretical modelling further demonstrate that this behaviour is explained by the different binding and unbinding rates of both integrin types to fibronectin. Moreover, rigidity sensing through differences in integrin bond dynamics applies both when integrins bind separately and when they compete for binding to fibronectin.
authors.affiliation: 1] Centre for Tumour Biology Barts Cancer Institute-a Cancer Research UK Centre of Excellence, Queen Mary, University of London, London EC1M 6BQ, UK [2] Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Elosegui-Artola
authors.affiliation: Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain.
authors.forename: Elsa
authors.initials: E
authors.lastname: Bazellières
authors.affiliation: Centre for Tumour Biology Barts Cancer Institute-a Cancer Research UK Centre of Excellence, Queen Mary, University of London, London EC1M 6BQ, UK.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Allen
authors.affiliation: CEIT and TECNUN (University of Navarra), 20018 Donostia-San Sebastian, Spain.
authors.forename: Ion
authors.initials: I
authors.lastname: Andreu
authors.affiliation: Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain.
authors.forename: Roger
authors.initials: R
authors.lastname: Oria
authors.affiliation: Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain.
authors.forename: Raimon
authors.initials: R
authors.lastname: Sunyer
authors.affiliation: Centre for Tumour Biology Barts Cancer Institute-a Cancer Research UK Centre of Excellence, Queen Mary, University of London, London EC1M 6BQ, UK.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Gomm
authors.affiliation: Centre for Tumour Biology Barts Cancer Institute-a Cancer Research UK Centre of Excellence, Queen Mary, University of London, London EC1M 6BQ, UK.
authors.forename: John F
authors.initials: JF
authors.lastname: Marshall
authors.affiliation: Centre for Tumour Biology Barts Cancer Institute-a Cancer Research UK Centre of Excellence, Queen Mary, University of London, London EC1M 6BQ, UK.
authors.forename: J Louise
authors.initials: JL
authors.lastname: Jones
authors.affiliation: 1] Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain [2] University of Barcelona, 08028 Barcelona, Spain [3] Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Trepat
authors.affiliation: 1] Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain [2] University of Barcelona, 08028 Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Roca-Cusachs
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological; D019030:Receptors, Vitronectin / Q000235:genetics / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D005353:Fibronectins; D016023:Integrins; D019030:Receptors, Vitronectin; C094340:integrin alphavbeta1; C073878:integrin alphavbeta6