Enhanced Concanavalin A Binding to Preorganized Mannose Nanoarrays in Glycodendrimersomes Revealed Multivalent Interactions

Abstract

The effect of the two-dimensional glycan display on glycan-lectin recognition remains poorly understood despite the importance of these interactions in a plethora of cellular processes, in (patho)physiology, as well as its potential for advanced therapeutics. Faced with this challenge we utilized glycodendrimersomes, a type of synthetic vesicles whose membrane mimics the surface of a cell and offers a means to probe the carbohydrate biological activity. These single-component vesicles were formed by the self-assembly of sequence-defined mannose-Janus dendrimers, which serve as surrogates for glycolipids. Using atomic force microscopy and molecular modeling we demonstrated that even mannose, a monosaccharide, was capable of organizing the sugar moieties into periodic nanoarrays without the need of the formation of liquid-ordered phases as assumed necessary for rafts. Kinetics studies of Concanavalin A binding revealed that those nanoarrays resulted in a new effective ligand yielding a ten-fold increase in the kinetic and thermodynamic constant of association.