Functional disorder and phase separation in cellular compartmentalization

Ever since the discovery of structural disorder, the functional merits of intrinsically disordered proteins/regions (IDPs/IDRs) are increasingly appreciated, yet the recognition that disordered proteins are key to assembling biomolecular condensates (BCs) has been a gamechanger in both fields. Recently, the study of their roles in the underlying process of liquid-liquid phase separation (LLPS) has become a central pillar of cell biology, material science, drug development, and biotechnology. Here, we discuss in detail artificial intelligence (AI)-driven integrative modeling and prediction of structural ensembles of IDPs and condensates, the role of the organization of cellular material into condensates in serving as electrochemical hubs, and the paradigm of condensate aging in disease. We also elucidate the prospects of creating synthetic organelles as programmable platforms for bio-inspired materials.