title: Ideal, catch, and slip bonds in cadherin adhesion.
abstract: Classical cadherin cell-cell adhesion proteins play key morphogenetic roles during development and are essential for maintaining tissue integrity in multicellular organisms. Classical cadherins bind in two distinct conformations, X-dimer and strand-swap dimer; during cellular rearrangements, these adhesive states are exposed to mechanical stress. However, the molecular mechanisms by which cadherins resist tensile force and the pathway by which they convert between different conformations are unclear. Here, we use single molecule force measurements with an atomic force microscope (AFM) to show that E-cadherin, a prototypical classical cadherin, forms three types of adhesive bonds: catch bonds, which become longer lived in the presence of tensile force; slip bonds, which become shorter lived when pulled; and ideal bonds that are insensitive to mechanical stress. We show that X-dimers form catch bonds, whereas strand-swap dimers form slip bonds. Our data suggests that ideal bonds are formed as X-dimers convert to strand-swap binding. Catch, slip, and ideal bonds allow cadherins to withstand tensile force and tune the mechanical properties of adhesive junctions.
authors.affiliation: Department of Physics and Astronomy, Iowa State University, Ames, IA 50011, USA.
authors.forename: Sabyasachi
authors.initials: S
authors.lastname: Rakshit
authors.forename: Yunxiang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kristine
authors.initials: K
authors.lastname: Manibog
authors.forename: Omer
authors.initials: O
authors.lastname: Shafraz
authors.forename: Sanjeevi
authors.initials: S
authors.lastname: Sivasankar
mesh_terms: D022005:Adherens Junctions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D015820:Cadherins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D018625:Microscopy, Atomic Force / Q000379:methods; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary
chemical_list: D015820:Cadherins