Catch Bond Interaction Between Glycosaminoglycans and Cell Surface Sulfatase Sulf1

Abstract

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. Interestingly, the transition between the two states 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.