Spontaneous enrichment of client molecules at phase boundaries of biomolecular condensates

The interface of biomolecular condensates plays a critical role in regulating many biochemical processes, such as protein aggregation and enzymatic activity. Targeted modulation of these interfaces offers a promising route for engineering condensates and correcting aberrant behaviors. However, the physical principles underlying the preferential localization of molecules at condensate interfaces are poorly understood. In this study, we develop an analytical theory for the enrichment of client molecules at the interface of phase-separated systems. We derive minimal conditions for interfacial localization based on pairwise interaction parameters. Our results reveal a general mechanism for passive interface-driven enrichment, which could guide the design of macromolecules that localize at the interface of biomolecular condensates.