Rational design of multicomponent condensates

Biology provides numerous examples of phase-separated protein and nucleic acid condensates, which establish distinct compartments for spatially organizing biomolecules within living cells. This mechanism of spatial organization relies on the ability of biomolecular systems to produce complex phase diagrams by tuning the interactions among molecules in a multicomponent mixture. To reproduce this behavior in synthetic systems, it is essential that we identify design rules that map the sequences of individual biomolecules to the emergent phase behavior of multicomponent systems. In this talk, I will describe recent theoretical and computational advances towards the goal of designing fully programmable, synthetic multiphase condensates. These results take the form of scaling relations that bound the complexity of phase diagrams that can be achieved in various biomolecular systems, as well as optimization algorithms for designing biomolecular mixtures that can spontaneously assemble into prescribed multiphase condensates. I will also discuss how nucleation pathways for biomolecular condensate assembly can be rationally designed, providing a mechanism for achieving precise spatiotemporal control of multicomponent, multiphase systems. Taken together, these design rules provide a deeper understanding of the limits of phase-separation-mediated spatial organization in biological systems and establish practical strategies for engineering fully programmable multiphase condensates.