Repulsion-Driven Layering in Polymer-Assisted Condensation

Abstract The hierarchical organization of multiphase biomolecular condensates into core-shell architectures is a fundamental problem in soft matter and biophysics. While classical explanations rely on hierarchies of interfacial tension (γ) between coexisting liquids, the ultralow tensions of condensates (0.1–1 µN/m) render such hierarchies potentially fragile. We introduce a robust assembly principle based on Polymer-Assisted Condensation (PAC), in which a single polymer species dictates the entire structure. The polymer nucleates a dense core by recruiting a condensation-incompetent protein (P1). A second incompetent protein (P2), which is repelled or otherwise thermodynamically disfavored from entering the polymer-rich core, is nonetheless recruited to the interface by weak attraction to P1, forming a stable shell. This effective repulsion-driven layering operates across a wide parameter space without requiring γ asymmetries and yields a robust structure that is impervious to concentration fluctuations and environmental perturbations. Phase-field modeling and molecular simulations establish this mechanism and capture key features of nucleolar organization. Our work reveals a general physical pathway for encoding spatial order in soft, multicomponent fluids. Competing Interest Statement The authors have declared no competing interest.