Unravelling the Secrets of Catechol-Cation Binding Synergy

Abstract

Aqueous electrolyte solutions, including physiological fluids and seawater, limit polymer adhesion to surfaces, yet the marine mussel produces protein glues that adhere robustly under water, even in highly adverse, such as contaminated, conditions. Adhesive mussel foot proteins commonly contain adjacent catecholic 3,4-dihydroxyphenylalanine (Dopa) and cationic lysine residues. Previous work has shown that the pairing of these residues results in significantly higher adhesion energies on inorganic surfaces than either Dopa or lysine alone. Two mechanisms for synergistic binding have been proposed: either lysine evicts adsorbed cations on the substrate, enabling subsequent binding of Dopa to the substrate; or paired Dopa and lysine residues bind simultaneously to the substrate. To evaluate the validity of these two mechanisms, a series of synthetic analogs of siderophores (bacterial iron chelators) was synthesized. The intramolecular spacing between catecholic and cationic moieties was systematically varied across the series. Adhesion forces/energies of monolayers of siderophore analogs confined between symmetrical mica surfaces were measured using a Surface Forces Apparatus (SFA). Our results show no statistically significant dependence of adhesion energy on intramolecular spacing. These results support the surface cation eviction mechanism for catechol-cation synergy, and suggest that proteins incorporating Dopa and lysine residues will display elevated adhesion energies even when the groups are not directly adjacent. The knowledge that catechol-cation binding synergy operates even when the moieties are spatially separated will guide future design of biologically inspired adhesives for medical, dental, and marine applications.