title: Demonstration of catch bonds between an integrin and its ligand.
abstract: 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 alpha(5)beta(1)-Fc fusion protein or membrane alpha(5)beta(1). Force prolonged bond lifetimes in the 10-30-pN range, a counterintuitive behavior called catch bonds. Changing cations from Ca(2+)/Mg(2+) to Mg(2+)/EGTA and to Mn(2+) caused longer lifetime in the same 10-30-pN catch bond region. A truncated alpha(5)beta(1) 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.
authors: Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors: Fang
authors: F
authors: Kong
authors: Andrés J
authors: AJ
authors: García
authors: A Paul
authors: AP
authors: Mould
authors: Martin J
authors: MJ
authors: Humphries
authors: Cheng
authors: C
authors: Zhu
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D039081:Integrin alpha5beta1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D000911:Antibodies, Monoclonal; D005353:Fibronectins; D039081:Integrin alpha5beta1; D008024:Ligands; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins