Interfacing Complex Coacervates with Natural Cells

Abstract Coacervates have been investigated as protocells or synthetic cells, as well as subcellular compartments for the creation of new materials, thus bridging the gap between living and non‐living systems in materials science, synthetic biology, and bioengineering. Given the design flexibility and simplicity of coacervates, along with the functionality and complexity of natural cells, the interfacing of complex coacervates with natural cells is considered significant for various biotechnological and biomedical applications. In this review, the fundamental mechanisms and underlying theories of coacervate systems are introduced. Recent efforts to interface coacervates with natural cells are summarized in three key scenarios: (i) the integration of coacervates with natural cell components for the living material assembly into protocells; (ii) communication between therapeutic synthetic cells and natural cells for drug delivery and cell repair; and (iii) the formation of intracellular condensates for metabolic regulation, followed by the regulation of their phase transitions for pathological elucidation. Finally, the potential of coacervate‐natural cell interfaces is discussed in the context of developing living/synthetic cell constructs, creating precise disease therapy strategies, and advancing programmable metabolic engineering networks.