Biomolecular condensates help organize biochemical processes in cells and synthetic cell analogues. Many condensates exhibit multiphase architectures, yielding compartments with distinct functions. However, how cells regulate the transformation between different multiphase architectures remains poorly understood. Here, we use multiphase coacervates as model condensates and present a new approach to control wetting and self-organization in multiphase coacervates by introducing a surface-active protein, α-synuclein (αSyn). αSyn can localize at the interface of uridine 5′-triphosphate (UTP)/poly-l-lysine (pLL)/oligo-l-arginine (R 10 ) multiphase coacervates and induce the transformation from nested droplets into partially wetted droplets. The exposed UTP/R 10 core coacervate droplets adhered to neighboring (shell) coacervates, forming structures similar to polymers and leading to a dynamic yet stable self-organized network of connected coacervates, that we call coacervate polymers. A theoretical model demonstrates that multiphase coacervates transition to partial wetting upon increasing the interfacial protein, consistent with experimental observations. When three neighboring coacervates are not aligned, surface tension straightens their arrangement similar to semiflexible polymers. This mechanism likely extends to larger structures, promoting chain formation while preventing fusion. Interestingly, diverse proteins were found to be surface active in multiphase coacervates: BSA, mCherry, and FtsZ all exhibited the same effect on multiphase coacervates partial wetting and organization. These findings suggest that interfacial proteins could be used by cells not only to stabilize condensates but also to control multiphase organization and to regulate the interaction between condensates.
Lu et al. (Sun,) studied this question.