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

Abstract

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.

Small Amphiphile‐Based Coacervation

“…Small amphiphile-based coacervates have been developed to build membrane-free coacervate microdroplets and hybrid protocells (e. g. multiphase coacervates and coacervate-inproteinosomes). [133,134] Self-assembly of fatty acids are commonly used as protocell model. Douliez et al developed a protocell based on the cationic and anionic surfactant mixtures.…”

Plant Cell-Inspired Membranization of Coacervate Protocells with a Structured Polysaccharide Layer

“…Membraneless coacervate microdroplets built from liquid–liquid phase separation (LLPS) have been extensively explored as protocells to unveil the origin of life . These membraneless microcompartments are constructed from simple molecules (e.g., ATP, oligopeptides, and polynucleotides) − capable of condensing biomolecules in the liquid-like phase, − generating a chemical gradient and facilitating chemical exchanges with the surrounding media. − Compared to plasma membrane-bound modern cells, coacervates sequestrated cargos with higher capacity and less selectivity. These drawbacks majorly resulted from the lack of an enclosed membrane.…”

Modulating liquid–liquid phase separation of FUS: mechanisms and strategies

“…1,2 Coacervate microdroplets based on LLPS were hypothesized to be relevant to the origin of life on the Earth by Oparin early in the 1930s. 3 In the past decade, coacervates have been studied extensively as protocells/synthetic cells due to their abilities of compartmentalization, 4,5 molecular enrichment, 6,7 reaction localization and enhancement, [8][9][10] active growth and division, [11][12][13][14] communication, 15,16 as well as artificial predation and phagocytosis, 17,18 protocell-natural cell interaction, 19,20 intracellular delivery, [21][22][23] protocell-based microactuator translocation, 24 and network-driven signal processing. 25 On the other side, the membraneless organelles based on intracellular condensation were known since the discovery of liquidlike P granules in dividing embryos of Caenorhabditis elegans by Hyman and Brangwynne et al 26 These liquid-like organelles without membranes as a typical intracellular compartmentalization form, such as nucleoli, Cajal bodies, stress granules, and P bodies, [27][28][29][30] are widely associated with cellular environmental sensing, 31 transcription regulation, 32,33 DNA damage repairing, 34 RNA processing and transportation, 35 neurotransmitter release, 36,37 innate immunity, 38 and the episode of neurodegenerative diseases in organisms.…”