(Dis-)appearance of liquid-liquid phase transitions in a heterogeneous activated patchy particle model and experiment

TL;DR

This study investigates how patch heterogeneity and ion binding energies influence the presence or absence of liquid-liquid phase separation in a model of globular proteins, revealing conditions that promote or suppress phase transitions.

Contribution

It demonstrates the critical role of patch heterogeneity and ion binding energies in controlling liquid-liquid phase separation, providing new insights into phase behavior in biological systems.

Findings

Ion binding energy determines phase separation presence.

Heterogeneous patches can suppress or promote LLPS.

Results explain ion-dependent phase behavior in protein solutions.

Abstract

The ion-activated patchy particle model is an important theoretical framework to investigate the phase behaviour of globular proteins in the presence of multivalent ions. In this work, we study and highlight the influence of patch heterogeneity on the extension, appearance and disappearance of the liquid-liquid coexistence region of the phase diagram. We demonstrate that within this model the binding energy between salt ions and patches of different type is a key factor in determining the phase behavior. Specifically, we show under which conditions liquid-liquid phase separation (LLPS) in these systems can appear or disappear for varying binding energy and ion-mediated attraction energy between ion-occupied and unoccupied patches. In particular we address the influence of the patch type dependence of these energies on the (dis)appearance of LLPS. These results rationalize our new results on ion-dependent liquid-liquid phase separation in solutions of bovine serum albumine with trivalent cations. In comparison with models with non-activated patches, where the gas-liquid transition disappears when the number of patches approaches two, we find the complementary mechanism that ions may shift the attractions from stronger to weaker patches (with an accompanying disappearance of the transition), if their binding energy to the patches changes. The results have implications for the understanding of charge-driven LLPS in biological systems and its suppression.