Liquid–Liquid Phase Separation of Peptide-Based Biomacromolecules: Mechanisms, Responsive Factors, and Biomedical Applications

Liquid–liquid phase separation (LLPS) drives the formation of biomolecular coacervates, which play important roles in cellular organization and disease development. In this review, the LLPS properties of proteins and peptides are systematically summarized, specifically on coacervate classification and sequence-based molecular design principles. These emphasize the importance of synergistic intermolecular forces in governing phase separation. Kinetically, the LLPS-mediated coalescence process in terms of nucleation barriers and further self-assembly is analyzed. The precise regulations of coacervate material properties by environmental factors are evaluated, including pH, ionic strength, redox potential, and enzymes. In applications, these dynamic systems demonstrate reversible dissociation, liquid-to-solid phase transitions, and good biocompatibility, which enable them to be developed as biomaterials for bioadhesives, microreactors, drug delivery, and optical signals. The fundamental characteristics of protein/peptide coacervates are bridged to their biomedical applications in this review, highlighting the potential of these materials in the development of scientific research and clinical translation.