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

Meng Liu,Giuseppe Battaglia,Edoardo Scarpa,Stefano Angioletti-Uberti,Miguel Sipin,Azzurra Apriceno,Alessandro Poma,Gabriele Marchello,Laura Rodriguez-Arco

doi:10.1038/s41467-020-18603-5

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.

Highlights

From viruses to nanoparticles, constructs functionalized with multiple ligands display peculiar binding properties that only arise from multivalent effects
We introduce here the concept of range selectivity, whereby a ligandcoated object binds a receptor-functionalised surface only when the latter has a number of receptors within a specific range, but neither below it nor, more strikingly, above it
Our analysis was based on a combination of a statistical mechanical model for ligand–receptor-mediated interactions[6,13] and a linear form for the repulsive energy, as extensively explained this phenomenon can be observed for a broad range of choices for this latter contribution

Summary

Introduction

Constructs functionalized with multiple ligands display peculiar binding properties that only arise from multivalent effects. In 2011, the microscopic origins of this behaviour have been explained by Martinez–Veracoecha and Frenkel[6], using an analysis rooted in statistical mechanics that highlighted the importance of the combinatorial binding entropy due to the various binding patterns achievable when multiple ligands and receptors are present These results have been validated several times, both by Monte Carlo calculations as well as by experimental data on different multivalent systems, thereby highlighting their generality[2,4,5,6,9,10,11]. In this article, using a combination of theory, numerical modelling and experiments, we present a qualitatively different type of selective targeting which arises in systems where attraction is dominated by the formation of ligand–receptor bonds: the ability, under appropriate conditions, to only bind to targets where the receptor density is within a certain range, but not below nor above

Methods

Results

Conclusion