ABSTRACT
Multivalent protein-protein and protein-RNA interactions are the drivers of biological phase separation. Bio-condensates typically contain a dense network of multiple proteins and RNAs, yet the role of overlapping molecular interactions in regulating the condensate composition and structure is not well understood. Employing a ternary system comprising of a prion-like polypeptide (PLD), arginine-rich polypeptide (RLD), and RNA, here we show that competition between the PLD and RNA for a single shared partner, the RLD, leads to PLD–RLD demixing and spontaneous formation of biphasic condensates. Combining experiments with simulations, we show that the topology of coexisting condensates is regulated via mixture composition and the nature of protein-protein and protein-RNA interactions, giving rise to a diverse set of multiphasic patterns including completely separated, partially and completely engulfed droplet morphologies, and Janus droplets. Our findings provide a minimal set of physical rules that govern the composition and spatial organization of multicomponent and multiphasic bio-condensates.
Competing Interest Statement
The authors have declared no competing interest.