Abstract

Intracellular biopolymer solutions, such as the cytosol and the nucleoplasm, can demix to form a wide variety of phase-separated condensates. Since a single intracellular compartment may feature multiple coexisting condensates with distinct compositions, it is natural to ask how reliably such complex phase behavior can be “programmed” into a biopolymer solution containing hundreds of components. Here we describe a theoretical model of phase separation in which components may be shared among multiple immiscible condensates. Combining convex optimization techniques and molecular simulation, we demonstrate that a surprisingly large number of such condensates can be programmed by rationally tuning the intermolecular interactions. This approach reveals general rules governing the phase behavior of multicomponent systems and establishes an efficient method for designing complex mixtures that phase separate into condensates with prescribed compositions.