Design principles for super selectivity using multivalent interactions

TL;DR

This paper presents a theoretical framework and design principles for achieving super-selectivity in multivalent particle interactions, enabling highly sensitive and tunable binding to target surfaces based on receptor density.

Contribution

It introduces a simple analytical model and design rules for optimizing multivalent interactions to achieve super-selectivity, advancing understanding of multivalent binding mechanisms.

Findings

Multivalent interactions can be highly sensitive to receptor density.

A simple analytical model predicts binding strength from physiochemical parameters.

Design rules enable the creation of highly selective multivalent systems.

Abstract

Multivalent particles have the ability to form multiple bonds to a substrate. Hence, a multivalent interaction can be strong, even if the individual bonds are weak. However, much more interestingly, multivalency greatly increases the sensitivity of the particle-substrate interaction to external conditions, resulting in an ultra-sensitive and highly non-linear dependence of the binding strength on parameters such as temperature, pH or receptor concentration. In this chapter we focus on super-selectivity: the high sensitivity of the strength of multivalent binding to the number of accessible binding sites on the target surface. For example, the docking of a multivalent particle on a cell-surface can be very sensitive (super-selective) to the concentration of the receptors to which the multiple ligands can bind. We present a theoretical analysis of systems of multivalent particles and describe the mechanism by which multivalency leads to super-selectivity. We introduce a simple analytical model that allows us to predict the overall strength of interactions based on physiochemical characteristics of multivalent binders. Finally, we formulate a set of simple design rules for multivalent interactions that yield optimal selectivity.