Aging-Directed Structural Evolution of In Situ Formed Polymeric Coacervates and Their Applications in Constructing Hierarchical Assemblies

Liquid–liquid phase separation (LLPS) represents a metastable state that undergoes natural aging, ultimately evolving into either physiological arrested states or pathological amyloid fibrils. However, the influence of the aging process on the structural evolution of macromolecular condensates remains poorly understood. In this study, we demonstrate that the synthetic active coacervates formed through polymerization-induced self-coacervation (PISC) serve as an ideal biomimetic platform to investigate these aging dynamics. By precisely modulating the aging pathways of in situ formed active coacervates, we reveal the critical role of liquid-to-solid transition (LST) kinetics in shaping the structural evolution of metastable coacervates. We find that slow solidification leads to surface solidification, resulting in a nonequilibrium solid shell. An intermediate LST rate promotes the growth of amyloid-like fibrils from the surfaces of liquid droplets, while excessive solidification hinders fibril development and leads to the formation of solid aggregates. Moreover, we also find that the structural evolution of these metastable droplets can even be steered by tuning their aging pathways. Coupling fibril growth with an evaporation-induced dehydration process promotes airflow-oriented fibril growth, facilitating the formation of three-dimensional solid particles with diverse morphologies, including echinate spherical particles and asymmetrical flower-like assemblies─structures that are typically difficult to synthesize through traditional molecular self-assembly methods. This study offers new insights into the relationship between aging dynamics and pathways and the resulting architectural structures, highlighting the potential for preparing hierarchical assemblies through the manipulation of the aging process.