Surface Ligand Density Switches Glycovesicles between Monomeric and Multimeric Lectin Recognition

Abstract

Carbohydrate‐protein interactions define a multitude of cellular recognition events. We present herein synthetic glycovesicles as cell‐surface mimics in order to switch the nature of lectin recognition. The covalent glycovesicles, constituted with diacetylene monomers of various ligand densities at their surfaces, are prepared through photo‐polymerization. Vesicles with sparsely imbedded ligands engage in a lectin interaction leading to the formation of a dense, crosslinked multimeric complex. On the other hand, vesicles with many ligands, or completely covered with them, switch the lectin interaction to form a fully soluble monomeric complex, without crosslinking. Nanomolar dissociation constants govern these interactions, as assessed by a ligand‐displacement assay. The study demonstrates the switching nature – between monomeric and multimeric – of the interaction as a function of ligand density in the vesicles; the results are directly relevant to understanding such a phenomenon occurring at cell surfaces.

Surface Density of Ligands Controls In‐Plane and Aggregative Modes of Multivalent Glycovesicle‐Lectin Recognitions

“…It is pertinent to compare the observations of the ligand‐lectin interactions in the trimannoside glycovesicle with that in monomannoside glycovesicles conducted earlier [41] . The lower density glycovesicles, as in 10 % sugar density surface, show lower hydrodynamic diameters ( D h ) and the same progressively increase as the sugar density increase, in both mono‐ and trimannoside glycovesicles (Table 3).…”

“…When using glycovesicles as the analytes, a very weak dissociation of vesicles from the surface was encountered, thereby preventing a direct evaluation of the interaction. An alternate indirect method of the competitive binding assay was undertaken in order to identify the binding affinities [41,55–57] . This assay is based on utilizing lectin which is pre‐saturated with glycovesicles as the analyte passing over the mannose‐immobilized surface.…”

“…Estimation of IC 90 , namely, the concentration of the vesicles required for 90 % inhibition of the Con A to bind immobilized mannose, was undertaken in the present study. For the inhibition studies, the mannose monosaccharide glycolipid was immobilized onto the HPA chip through the intercalation mechanism [41] . The pre‐incubated mixtures of Con A solutions (57 nm) were prepared with increasing concentrations of either trisaccharide glycolipid vesicle or methyl mannoside.…”

“…Critical to the intra‐ vs inter‐cellular interaction is the threshold sugar density at the surface of the glycovesicle. In an earlier study, we undertook to study synthetic glycovesicles embedded with mono‐mannopyranoside and ligand density‐driven intra‐ and intervesicular interactions with lectin Con A [41] . A gradation of sugar densities at the surface emerged, by which lower sugar density surfaces preferred intervesicular interactions, whereas glycovesicles constituted with most sugar lipids underwent intravesicular sugar‐lectin interaction.…”