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

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.