Peptide Coacervates: Formation, Mechanism, and Biological Applications

Biomolecular coacervates, dynamic compartments formed via liquid-liquid phase separation (LLPS), are essential for orchestrating intracellular processes and have emerged as versatile tools in bioengineering. Peptides, with their modular amino acid sequences, exhibit unique potential in coacervate design due to their ability to undergo LLPS while offering precise control over molecular architecture and environmental responsiveness. Their simplicity, synthetic accessibility, and tunability make peptide-based coacervates particularly attractive for biomedical and materials applications. However, the formation and stability of these systems depend on a delicate balance of intrinsic factors (e.g., sequence charge, hydrophobicity, and chain length) and extrinsic conditions (e.g., pH, ionic strength, and temperature), necessitating a deeper understanding of their interplay. This review synthesizes recent advances in the molecular mechanisms driving peptide coacervation, emphasizing how sequence design and environmental cues govern phase behavior. We further highlight groundbreaking applications, from drug delivery platforms to protocell mimics, and discuss strategies to translate mechanistic insights into functional materials. By bridging fundamental principles with innovative applications, this work aims to accelerate the development of peptide coacervates as programmable, multifunctional systems, offering a roadmap for next-generation biochemical technologies.