The Role of Receptor Uniformity in Multivalent Binding

[Image: see text] 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 nanoparticles but also introduce a new perspective in understanding biological processes involving multivalency.