Recruitment of Receptors and Ligands in a Weakly Multivalent System with Omnipresent Signatures of Superselective Binding

Recruitment of receptors at membrane interfaces is essential in biological recognition and uptake processes. The interactions that induce recruitment are typically weak at the level of individual interaction pairs, but are strong and selective at the level of recruited ensembles. Here, a model system is demonstrated, based on the supported lipid bilayer (SLB) that mimics the recruitment process induced by weakly multivalent interactions. The weak (mm range) histidine-nickel-nitrilotriacetate (His₂-NiNTA) pair is employed owing to its ease of implementation in both synthetic and biological systems. The recruitment of receptors (and ligands) induced by the binding of His₂-functionalized vesicles on NiNTA-terminated SLBs is investigated to identify the ligand densities necessary to achieve vesicle binding and receptor recruitment. Threshold values of ligand densities appear to occur in many binding characteristics: density of bound vesicles, size and receptor density of the contact area, and vesicle deformation. Such thresholds contrast the binding of strongly multivalent systems and constitute a clear signature of the superselective binding behavior predicted for weakly multivalent interactions. This model system provides quantitative insight into the binding valency and effects of competing energetic forces, such as deformation, depletion, and entropy cost of recruitment at different length scales.