Control of superselectivity by crowding in three-dimensional hosts

TL;DR

This paper explores how molecular crowding in three-dimensional structures can induce superselectivity in binding interactions, revealing a novel mechanism that contrasts with surface-based systems and is robust across various parameters.

Contribution

It demonstrates that inert crowding agents can enhance or induce superselectivity in 3D environments, a phenomenon not previously characterized in such systems.

Findings

Crowding agents can significantly enhance superselectivity.

Superselectivity is robust to changes in valency, linker length, and binding strength.

Crowding initially suppresses binding but facilitates multivalent interactions.

Abstract

Motivated by the fine compositional control observed in membraneless droplet organelles in cells, we investigate how a sharp binding-unbinding transition can occur between multivalent client molecules and receptors embedded in a porous three-dimensional structure. In contrast to similar superselective binding previously observed at surfaces, we have identified that a key effect in a three-dimensional environment is that the presence of inert crowding agents can significantly enhance or even introduce superselectivity. In essence, molecular crowding initially suppresses binding via an entropic penalty, but the clients can then more easily form many bonds simultaneously. We demonstrate the robustness of the superselective behavior with respect to client valency, linker length and binding interactions in Monte Carlo simulations of an archetypal lattice polymer model.