Coacervate Microdroplets as Synthetic Protocells for Cell Mimicking and Signaling Communications

Abstract Synthetic protocells are minimal systems that mimic certain properties of natural cells and are used to research the emergence of life from a nonliving chemical network. Currently, coacervate microdroplets, which are formed via liquid–liquid phase separation, are receiving wide attention in the context of cell biology and protocell research; these microdroplets are notable because they can provide liquid‐like compartment structures for biochemical reactions by creating highly macromolecular crowded local environments. In this review, an overview of recent research on the formation of coacervate microdroplets through phase separation; the design of coacervate‐based stimuli‐responsive protocells, multichamber protocells, and membranized protocells; and their cell mimic behaviors, is provided. The simplified protocell models with precisely defined and tunable compositions advance the understanding of the requirements for cellular structure and function. Efforts are then discussed to establish signal communication systems in protocell and protocell consortia, as communication is a fundamental feature of life that coordinates matter exchanges and energy fluxes dynamically in space and time. Finally, some perspectives on the challenges and future developments of synthetic protocell research in biomimetic science and biomedical applications are provided.