Combinatorial entropy behaviour leads to range selective binding in ligand-receptor interactions

TL;DR

This paper introduces a statistical mechanical model explaining how multivalent ligand-receptor interactions can be engineered for range selectivity, binding only within a specific receptor number range, enhancing targeting precision.

Contribution

It provides a novel theoretical framework for understanding and designing multivalent constructs with range selectivity, supported by experimental validation.

Findings

Range selectivity depends on combinatorial entropy effects.

Model identifies parameter regions for effective range targeting.

Experimental data confirms the theoretical predictions.

Abstract

From viruses to nanoparticles, constructs functionalized with multiple ligands display peculiar binding properties that only arise from multivalent effects. Using statistical mechanical modelling, we describe here how multivalency can be exploited to achieve what we dub range selectivity, that is, binding only to targets bearing a number of receptors within a specified range. We use our model to characterise the region in parameter space where one can expect range selective targeting to occur, and provide experimental support for this phenomenon. Overall, range selectivity represents a potential path to increase the targeting selectivity of multivalent constructs.