title: Talin tension sensor reveals novel features of focal adhesion force transmission and mechanosensitivity.
abstract: Integrin-dependent adhesions are mechanosensitive structures in which talin mediates a linkage to actin filaments either directly or indirectly by recruiting vinculin. Here, we report the development and validation of a talin tension sensor. We find that talin in focal adhesions is under tension, which is higher in peripheral than central adhesions. Tension on talin is increased by vinculin and depends mainly on actin-binding site 2 (ABS2) within the middle of the rod domain, rather than ABS3 at the far C terminus. Unlike vinculin, talin is under lower tension on soft substrates. The difference between central and peripheral adhesions requires ABS3 but not vinculin or ABS2. However, differential stiffness sensing by talin requires ABS2 but not vinculin or ABS3. These results indicate that central versus peripheral adhesions must be organized and regulated differently, and that ABS2 and ABS3 have distinct functions in spatial variations and stiffness sensing. Overall, these results shed new light on talin function and constrain models for cellular mechanosensing.
authors.affiliation: Yale Cardiovascular Research Center, Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, Yale University, New Haven, CT 06511.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Yale Cardiovascular Research Center, Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, Yale University, New Haven, CT 06511.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Ouyang
authors.affiliation: Yale Cardiovascular Research Center, Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, Yale University, New Haven, CT 06511.
authors.forename: Koen
authors.initials: K
authors.lastname: Van den Dries
authors.affiliation: Beatson Institute for Cancer Research, Glasgow G20 0TZ, Scotland, UK.
authors.forename: Ewan James
authors.initials: EJ
authors.lastname: McGhee
authors.affiliation: Yale Cardiovascular Research Center, Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, Yale University, New Haven, CT 06511.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: School of Biosciences, University of Kent, Canterbury CT2 7NZ, England, UK.
authors.forename: Marie D
authors.initials: MD
authors.lastname: Anderson
authors.affiliation: Department of Physics, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Alexander
authors.initials: A
authors.lastname: Groisman
authors.affiliation: School of Biosciences, University of Kent, Canterbury CT2 7NZ, England, UK.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Goult
authors.affiliation: Beatson Institute for Cancer Research, Glasgow G20 0TZ, Scotland, UK.
authors.forename: Kurt I
authors.initials: KI
authors.lastname: Anderson
authors.affiliation: Yale Cardiovascular Research Center, Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, Yale University, New Haven, CT 06511 Department of Cell Biology, Yale University, New Haven, CT 06520 Department of Biomedical Engineering, Yale University, New Haven, CT 06520 martin.schwartz@yale.edu.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Schwartz
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D031541:Fluorescence Resonance Energy Transfer; D022001:Focal Adhesions; D040542:Mechanotransduction, Cellular; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D016608:Talin / Q000378:metabolism / Q000502:physiology*; D016596:Vinculin / Q000378:metabolism / Q000502:physiology
chemical_list: D016608:Talin; D016596:Vinculin