The purification of biomolecular condensates: Bottlenecks and strategies

Biomolecular condensates are large assemblies of proteins and nucleic acids that form distinct compartments inside the cell without being surrounded by a membrane. They form through multivalent interactions, are not stereospecifically defined, and can scale with component addition. By concentrating specific biomolecules at specific times and cellular locations, condensates play key roles in many processes, such as transcription, RNP assembly, cell cycle, DNA repair, and stress responses. Condensate biology greatly benefited from systematic analyses of their composition. However, condensates often have heterogenous sizes and are built on interaction networks that include stable and labile components. They also have highly variable compositions and dynamics. Their purification thus represents a significant challenge, and it necessitates extensive testing and adaptation of techniques originally designed for other applications. This article aims to synthesize the existing empirical knowledge on the extraction and purification of cellular condensates and analyze the challenges inherent to this field.