Transient Compartmentalization in Coacervates Driven by Chemically Fueled Autocatalysis and Interfacial Remodeling

Membraneless organelles (MLOs) exhibit hierarchical and dynamic architectures essential for cellular regulation, yet recreating such structural complexity synthetically remains a fundamental challenge. Here, we introduce a chemically fueled dissipative reaction network that programs the hierarchical evolution of coacervate droplets through coupled reactions, assembly, and interfacial editing. The system is built on a thiol-thioester exchange that autocatalytically generates surfactant micelles, which subsequently undergo electrostatic complexation to form liquid-like coacervates. A subsequent thiol-disulfide cascade produces an asymmetric aromatic surfactant (<b>6</b>) that selectively enriches at droplet interfaces via cation-π and π-π interactions. This interfacial adsorption triggers symmetry breaking and cavity nucleation within the droplets. Subsequent interfacial softening, fusion-driven reorganization, and kinetic trapping yield stable multicompartmental architectures, while hydrolysis-mediated dissipation ensures system reversibility. Our work establishes a minimal yet programmable chemical platform that integrates autocatalysis, liquid-liquid phase separation (LLPS), and interfacial remodeling to achieve spatiotemporal control over condensate morphology. Beyond offering a mechanistic model for dissipative phase separation, this system provides a versatile strategy to couple reaction networks with self-assembly, paving the way toward adaptive soft materials with life-like organizational complexity.