Dynamic Assembly of Viscoelastic Networks by Aqueous Liquid–Liquid Phase Separation and Liquid–Solid Phase Separation (AqLL‐LS PS2)

Abstract Living cells comprise diverse subcellular structures, such as cytoskeletal networks, which can regulate essential cellular activities through dynamic assembly and synergistic interactions with biomolecular condensates. Despite extensive efforts, reproducing viscoelastic networks for modulating biomolecular condensates in synthetic systems remains challenging. Here, a new aqueous two‐phase system (ATPS) is proposed, which consists of poly( N ‐isopropylacrylamide) (PNIPAM) and dextran (DEX), to construct viscoelastic networks capable of being assembled and dissociated dynamically to regulate the self‐assembly of condensates on‐demand. Viscoelastic networks are generated using liquid–liquid phase‐separated DEX droplets as templates and the following liquid‐to‐solid transition of the PNIPAM‐rich phase. The resulting networks can dissolve liquid fused in sarcoma (FUS) condensates within 5 min. This work demonstrates rich phase‐separation behaviors in a single ATPS through incorporating stimuli‐responsive polymers. The concept can potentially be applied to other macromolecules through other stimuli to develop materials with rich phase behaviors and hierarchical structures.