Demonstration of catch bonds between an integrin and its ligand

By F. Kong, Andrés J. García, A. Mould, M. Humphries, Cheng-Long Zhu. Journal of Cell Biology, 2009

698 citations recorded by the source corpus.

Binding of integrins to ligands provides anchorage and signals for the cell, making them prime candidates for mechanosensing molecules. How force regulates integrin–ligand dissociation is unclear. We used atomic force microscopy to measure the force-dependent lifetimes of single bonds between a fibronectin fragment and an integrin α5β1-Fc fusion protein or membrane α5β1. Force prolonged bond lifetimes in the 10–30-pN range, a counterintuitive behavior called catch bonds. Changing cations from Ca2+/Mg2+ to Mg2+/EGTA and to Mn2+ caused longer lifetime in the same 10–30-pN catch bond region. A truncated α5β1 construct containing the headpiece but not the legs formed longer-lived catch bonds that were not affected by cation changes at forces <30 pN. Binding of monoclonal antibodies that induce the active conformation of the integrin headpiece shifted catch bonds to a lower force range. Thus, catch bond formation appears to involve force-assisted activation of the headpiece but not integrin extension.

Subfields: Atomic and Molecular Physics, and Optics, Cell Biology, Immunology and Allergy

View Paper: https://www.semanticscholar.org/paper/a393fd38095534f73937445c31dde54d4fb52909

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Citations in the corpus

Mechanical Integration of Actin and Adhesion Dynamics in Cell Migration (2010, background): “For bonds between α5β1 integrin and its ECM ligand, fibronectin, the application of forces up to tens of picoNewtons prolongs the bond lifetime owing to force-induced changes in the conformation of the integrin head that are akin to activation (Kong et al. 2009).”
Dynamic molecular processes mediate cellular mechanotransduction (2011, neutral): “Other crucial linkages in mechanotransduction, such as fibronectin–integrin (α 5 β 1 integrin”
Harnessing Traction-Mediated Manipulation of the Cell-Matrix Interface to Control Stem Cell Fate (2010, background): “, and models that predict a biphasic relationship between applied force and bond lifetim”
Integrin-mediated mechanotransduction (2016, background): “…in their relaxed state bind to the tripeptide RGD (Arg-Gly-Asp) motif in the 10th type III module of fibronectin (FNI II10; Takagi et al., 2003), whereas they additionally engage the synergy site in FNI II9 under tensile load to form a catch bond (Friedland et al., 2009; Kong et al., 2009).”
The myofibroblast: paradigm for a mechanically active cell. (2010, background): “In another study, application of force to single a5b1 integrins using AFM cantilevers grafted with FN fragments increased the bond lifetime—a defining feature of catch bonds (Kong et al., 2009).”