Molecular determinants of protein-based coacervates

Protein–polyelectrolyte coacervates have gained interest for their potential to stabilize proteins or function as adhesives and their biological implications in the formation of membraneless organelles. To effectively design these materials or predict their biological formation, knowledge of the macromolecular properties that dictate phase separation is required. This review highlights recent advances in the understanding of molecular determinants of protein–polyelectrolyte phase behavior. Properties that promote the phase separation of protein–polyelectrolyte pairs are covered from the perspective of synthetic systems and simplified biological condensates. Prominent factors that determine coacervate formation and material properties include nonspecific intermolecular interactions, as well as specific biological interactions and structures. Here, we summarize the essential roles of electrostatics, including charge magnitude and distribution, (bio)polymer chemistry and structure, and post-translational modifications to protein phase separation in both a synthetic and cellular context.