Partial demixing of RNA-protein complexes leads to intradroplet patterning in phase-separated biological condensates.

An emerging mechanism for intracellular organization is liquid-liquid phase separation (LLPS). Found in both the nucleus and the cytoplasm, liquidlike droplets condense to create compartments that are thought to promote and inhibit specific biochemistry. In this work, a multiphase, Cahn-Hilliard diffuse interface model is used to examine RNA-protein interactions driving LLPS. We create a bivalent system that allows for two different species of protein-RNA complexes and model the competition that arises for a shared binding partner, free protein. With this system we demonstrate that the binding and unbinding of distinct RNA-protein complexes leads to diverse spatial pattern formation and dynamics within droplets. Both the initial formation and transient behavior of spatial patterning are subject to the exchange of free proteins between RNA-protein complexes. This study illustrates that spatiotemporal heterogeneity can emerge within phase-separated biological condensates with simple binding reactions and competition. Intradroplet patterning may influence droplet composition and, subsequently, cellular organization on a larger scale.