Programmable phase behavior in biopolymer solutions

Intracellular biopolymer solutions, such as the cytosol and the nucleoplasm, can demix to form a wide variety of phase-separated condensates. A single intracellular compartment may in fact feature multiple coexisting condensates with distinct compositions. These observations raise the question of how reliably such complex phase behavior can be "programmed" into a biopolymer solution containing thousands of components. Here we describe a theoretical model of phase separation in which components may be shared among multiple condensates. Theoretical analysis and molecular simulations demonstrate that a large number of condensates can be programmed by tuning the intermolecular interactions and subsequently assembled by selective nucleation at heterogeneous nucleation sites. When condensates share components, the number of compositionally distinct condensates that can be reliably programmed grows superlinearly with the number of components in the mixture. As a result, we propose that biological systems may take advantage of similar combinatorial strategies to broaden the range of useful behaviors that can be achieved via phase separation.