A minimal model for liquid-liquid phase separation and aging of chemically reactive macromolecular mixtures

Mixtures of several macromolecular species can lead to the formation of higher-order structures that often display non-ideal mixing behavior. In this work, we propose a minimal model of a quaternary system which considers the formation of a complex via a chemical reaction involving two macromolecular species; the complex may then phase separate from the buffer and undergo a further transition into a gel-like state over time. First, a ternary phase diagram that captures the volume fraction of each species and phases at equilibrium is constructed. Specifically, we investigate how physical parameters such as stoichiometric coefficients, molecular sizes and interaction parameters affect LLPS and aging. Finally, we analyze the thermodynamic stability of the two-phase system and identify the spinodal regions, and outline the generalization of our approach to reactive biomolecular systems with an arbitrary number of components.