Phase separation controlled by molecular transitions

Phase separation and transitions among molecular states are ubiquitous in living cells. Such transitions can be governed by thermodynamics or actively controlled by biological fuel. It remains largely unexplored how the behavior of phase separating systems with molecular transitions differs between thermodynamic equilibrium and cases where detailed balance of the rates is broken due to the presence of fuel. Here, we derive a minimal model of a phase-separating ternary mixture where two components can convert into each other. We find that molecular transitions can lead to a lower critical dissolution temperature below which phase-separated droplets dissolve. Moreover, we find a discontinuous thermodynamic phase transition in the composition of the dense phase if both converting molecules attract themselves with similar interaction strength. Accounting for detailed-balance broken molecular transitions releases the system from Gibbs phase rule constraint, facilitating rapid changes in droplet composition by fuel quenches for a larger range of intermolecular interactions. Our findings showcase the potential of phase separation with molecular transitions as a mechanism to control properties of intra-cellular condensates via discontinuous switches in droplet composition.