Oral: Role of von Willebrand Factor Type D Like Domains for Mucin Adhesion

Mucin is a high-molecular-weight glycoprotein that covers wet epithelia of mammalians. Mucin acts as a versatile biolubricant and reduces friction and wear by generating a sacrificial layer and establishing hydration lubrication. It consists of a terminal hydrophobic region, i.e., non-glycosylated and partially folded domains comprising von Willebrand Factor (VWF) type D like domains, and a polyanionic hydrophilic core region, which is highly glycosylated.[1-3]

We use Atomic Force Microscopy (AFM) based Single Molecule Force Spectroscopy (SMFS) under near-physiological conditions to study the detachment of single mucins on solid substrates. This becomes possible by covalent binding of a single molecule to an AFM cantilever tip.[4,5] We reveal the force-induced partial unfolding of the VWF type D like domains and deliver their unfolding rates and free energy barriers. These domains serve to dissipate energy, i.e., they act as sacrificial bonds and enhance mucin adhesion. Our investigations serve to understand adhesion mechanisms of complex biomolecules and to design future glycoprotein mimetics and biomimetic surface coatings.

References:

[1] M. Marczynski et al., Colloids Surf. B: Biointerfaces, 2020, 187, 110614.

[2] B. T. Käsdorf et al., Biomacromolecules, 2017, 18(8), 2454-2462.

[3] G. Petrou and T. Crouzier, Biomater. Sci., 2018, 6, 2282–2297.

[4] Kolberg et al., J. Vis. Exp., 2020, 157, e60934.

[5] Lallemang et al., Nanoscale, 2022, 14, 3768-3776.