Redox‐Controlled, Sequential Self‐Sorting of Supramolecular Assemblies in Model Protocells

Abstract Self‐sorting of cellular components is essential for maintaining order and function in living systems, enabling complex processes to operate seamlessly. Emulating such self‐sorting in synthetic self‐assembly, however, has conventionally relied on structural or chirality mismatches of monomers yielding self‐sorted systems under thermodynamic conditions. In contrast, reaction‐coupled, kinetically controlled self‐assembly, ubiquitous in biological systems, is critical for achieving spatiotemporal characteristics. Extending this principle to temporally self‐sorted synthetic assemblies is key to developing multi‐component biomimetic systems. Herein, we present a strategy towards this direction, to achieve sequential self‐sorting of supramolecular assemblies through differences in the chemical‐reactivity of monomers, coupled to redox‐reactions. This approach exploits the distinct redox potentials of monomers to achieve precise temporal‐control over self‐sorting, while inherent structural mismatches among monomers ensure the kinetic stability of self‐sorted state. Reduction reactions transiently disrupt their assemblies into dormant inactive monomeric states, while subsequent kinetically controlled reassembly occurs via reversible oxidation reactions. Finally, utilizing this sequential self‐sorting, we aim to mimic multicomponent cellular self‐organization by demonstrating the kinetically controlled growth of self‐sorted structures in the presence of model protocells, using lipid vesicles as compartments. Although spatial‐distribution remains non‐selective, the dormant monomeric states facilitate monomer encapsulation and the unprecedented stepwise‐formation of self‐sorted assemblies within model protocells.