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BP: Fachverband Biologische Physik
BP 20: Cell adhesion, mechanics and migration I
BP 20.1: Topical Talk
Dienstag, 1. April 2014, 13:00–13:30, HÜL 386
Catch bond interaction between glycosaminoglycans and cell surface sulfatase Sulf1 — Alexander Harder1, Ann-Kristin Moeller1, Fabian Milz2, Phillipp Neuhaus2, Volker Walhorn1, Thomas Dierks2, and •Dario Anselmetti1 — 1Experimental Biophysics, Physics Faculty, Bielefeld University, D-33615 Bielefeld, Germany. — 2Biochemistry I, Faculty of Chemistry, Bielefeld University, D-33615 Bielefeld, Germany.
In biological adhesion, the biophysical mechanism of specific non-covalent biomolecular interaction can be divided in slip- and catch-bonds, respectively. Conceptually, slip bonds exhibit reduced bond lifetime under increased external loads whereas catch-bonds, in contrast, increased lifetime for a certain force interval. Since 2003, a handful of biological systems such as the adhesive proteins P-Selectin and FimH have been identified to display catch bond properties.
Upon investigating the specific interaction between the unique hydrophilic domain (HD) of human cell-surface sulfatase Sulf1 against the native glycosaminoglycan (GAG) target heparan sulfate (HS) by single molecule force spectroscopy (SMFS), we found clear evidence of catch-bond behavior in this system. The HD, about 320 amino acids long and strongly positive charged, and the GAG-polymers, composed of up to 200 disaccharide units, were quantitatively investigated with atomic force microscopy (AFM) based dynamic force spectroscopy (DFS) as well as force clamp spectroscopy (FCS). The observed catch bond character of HD against GAGs was found to be specifically related to the GAG 6-O-sulfation site. Therefore, this behavior can also be found in HS-related GAGs like heparin and (to a lesser extent) dermatan sulfate whereas in contrast, only slip bond binding can be observed in a GAG system where these sites are explicitly lacking. Our observed catch bond binding data can be interpreted within the theoretical framework of a force mediated transition between two slip bond regimes modelled by a switchover within a double-well energy landscape. Interestingly, the transition occurs in a force interval of only 5 Piconewtons while the life-time of the adhesion bond increases approximately 5-fold for heparan sulfate and heparin.