The role of receptor uniformity in multivalent binding

TL;DR

This paper reveals that receptor uniformity enhances multivalent binding selectivity at intermediate energies, challenging previous beliefs that weaker binding always improves selectivity, with implications for biosensor design and biological understanding.

Contribution

It demonstrates through theory and simulations that receptor uniformity can maximize selectivity at intermediate binding energies, offering new insights into multivalent interactions.

Findings

Maximum selectivity occurs at intermediate binding energies for uniform receptors.

Receptor uniformity significantly increases multivalent binding selectivity.

The bound fraction's exponential dependence on receptor concentration is key to understanding selectivity.

Abstract

Multivalency is prevalent in various biological systems and applications due to the superselectivity that arises from the cooperativity of multivalent binding. Traditionally, it was thought that weaker individual binding would improve the selectivity in multivalent targeting. Here using analytical mean field theory and Monte Carlo simulations, we discover that for receptors that are highly uniformly distributed, the highest selectivity occurs at an intermediate binding energy and can be significantly greater than the weak binding limit. This is caused by an exponential relationship between the bound fraction and receptor concentration, which is influenced by both the strength and combinatorial entropy of binding. Our findings not only provide new guidelines for the rational design of biosensors using multivalent nano-particles but also introduce a new perspective in understanding biological processes involving multivalency.