Accelerated Ostwald ripening by chemical activity

Abstract: Phase separation of biomolecular condensates is ubiquitous in living cells, promoting colocalization of enzymes and their substrates as well as achieving membrane-free compartmentalization. Energy-consuming processes are routinely used to regulate biocondensate growth by opposing the thermodynamic tendency toward coarsening. At the same time, cells often use energy to instead accelerate thermodynamic processes. Here, we theoretically explore the possibility of utilizing chemical reactions to accelerate biocondensate coarsening. We combine Lifshitz-Slyozov theory with a reaction-diffusion approach, wherein particles interconvert between phase-separating and inert forms. We find that mass conservation restricts the volume growth to be linear in time (as in the passive case) despite activity, though if reactions are restricted to occur only outside droplets, the rate of Ostwald ripening can be increased by an arbitrarily large factor. Our acceleration theory is quantitatively supported by recent experiments on ripening in the presence of fueled interconversion reactions, under precisely the predicted conditions. We posit that the ability to induce rapid biocondensate coarsening can be advantageous in synthetic-biological contexts as a regulator of metabolic channeling.