Catch Bond Interaction between Cell-Surface Sulfatase Sulf1 and Glycosaminoglycans

Abstract

In biological adhesion, the biophysical mechanism of specific biomolecular interaction can be divided in slip and catch bonds, respectively. Conceptually, slip bonds exhibit a reduced bond lifetime under increased external force and catch bonds, in contrast, exhibit an increased lifetime (for a certain force interval). Since 2003, a handful of biological systems have been identified to display catch bond properties. Upon investigating the specific interaction between the unique hydrophilic domain (HD) of the human cell-surface sulfatase Sulf1 against its physiological 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, ∼320 amino acids long with dominant positive charge, and its interaction with sulfated GAG-polymers were quantitatively investigated using atomic force microscopy (AFM) based force clamp spectroscopy (FCS) and dynamic force spectroscopy (DFS). In FCS experiments, we found that the catch bond character of HD against GAGs could be attributed to the GAG 6-O-sulfation site whereas only slip bond interaction can be observed in a GAG system where this site is explicitly lacking. We interpreted the binding data within the theoretical framework of a two state two path model, where two slip bonds are coupled forming a double-well interaction potential with an energy difference of ΔE ≈ 9 kBT and a compliance length of Δx ≈ 3.2 nm. Additional DFS experiments support this assumption and allow identification of these two coupled slip-bond states that behave consistently within the Kramers-Bell-Evans model of force-mediated dissociation.

Interactions between the breast cancer-associated MUC1 mucins and C-type lectin characterized by optical tweezers

“…These lifetimes are in the same range as previously determined for other carbohydrate–protein interactions using AFM [42, 43] and OT [55]. As expected it is shorter than the lifetime of antibody-peptide interactions [56] as well as the interaction between cell-surface sulfatase Sulf1 and glycosaminoglycans [57]. Despite the similarity of both the binding strengths and the lifetimes of the MUC1(Tn) and MUC1(STn) interactions with MGL, a slightly lower x β value was determined for the MUC1(STn)–MGL system (Tables 2 and 3).…”

Phenomenological and microscopic theories for catch bonds

“…This too cannot be explained by the current model and might be important to consider in the future. As noted earlier, triphasic behavior has also been seen in the interactions of cell surface sulfatase and glycosaminoglycans (Harder et al, 2015), where the authors explained the data using the two-state model as formulated by BT Barsegov and Thirumalai, 2005. Finally, we should point out that unlike the only available microscopic theory, so far restricted to the selectin family (Chakrabarti et al, 2014), the phenomenological model can be used to quantitatively analyze all of the available data.…”

“…The predicted triphasic (slip-catch-slip) behavior should be generic although it appears that in many cases F min could be very small, thus preventing detection of the initial slip bond behavior. However, this triphasic behavior has been observed in an insightful experiment probing cell surface sulfatase and glycosaminoglycan interactions (Harder et al, 2015) (Fig. 2b), and also in an experiment on the von Willebrand factor (Kim et al, 2009).…”

“…The two-state model has been subsequently used to explain catch-slip data from a number of biological systems like the bacterial FimH adhesive protein (Thomas et al, 2006; Pereverzev et al, 2009), kinetochore-microtubule attachments (Akiyoshi et al, 2010), cell surface sulfatase and glycosaminoglycan interactions (Harder et al, 2015) and cadherin-catenin interactions (Buckley et al, 2014). Among all these experiments, the work by Akiyoshi et al on kinetochore-microtubule attachments (Akiyoshi et al, 2010) is a remarkable validation of the two-state model.…”

“…Catch bond data from (a) Kinetochore-microtubules (Akiyoshi et al, 2010) and (b) sulfatase-glycosaminoglycans (Harder et al, 2015). The filled circles are experimental data while the lines are fits using the general two-state model.…”