Directing Transition of Synthetic Protocell Models via Physicochemical Cues‐Triggered Interfacial Dynamic Covalent Chemistry

As the preliminary synthetic analogs of living cells, protocells with life‐like features serve as a versatile platform to explore the origin of life. Although protocells constructed from multiple components have been developed, the transition of primitive cellular compartments toward structural complexity and advanced function remains a scientific challenge. Herein, a programmable pathway is established to exploit a simple chemistry to construct structural transition of protocell models from emulsion droplets, nanocapsules to molecularly crowded droplets. The transitional process toward distinct cell‐like compartments is driven by interfacial self‐assembly of simple components and regulated by physicochemical cues (e.g., mechanical force, solvent evaporation, acid/base equilibrium) triggered dynamic covalent chemistry. These protocell models are further studied by comparing their compartmentalization behavior, sequestration efficiency, and the ability to enrich biomolecules (e.g., enzyme and substrate) toward catalytic reaction or biological activity within the compartments. The results showcase physiochemical cues‐driven programmable transition of life‐like compartments toward functionalization, and offer a new step toward the design of living soft materials.