Programmable ATP-Fueled DNA Coacervates by Transient Liquid-Liquid Phase Separation

Multivalency-driven liquid-liquid phase separation (LLPS) is essential for biomolecular condensates to facilitate spatiotemporal regulation of biological functions. Providing programmable model systems would help to better understand the LLPS processes in biology and furnish new types of compartmentalized synthetic reaction crucibles that exploit biological principles. Herein, we demonstrate a concept for programming LLPS using transient multivalency between ATP-driven sequence-defined functionalized nucleic acid polymers (SfNAPs), which serve as simple models for membraneless organelles. Critically, the prominent programmability of the DNA-based building blocks allows to encode distinct molecular recognitions for multiple multivalent systems, enabling sorted LLPS and, thus, multicomponent DNA coacervates. The ATP-driven coacervates are capable for multivalent trapping of micron-scale colloids and biomolecules to generate functions as emphasized for rate enhancements in enzymatic cascades. This work demonstrates ATP-driven multivalent coacervation as a valuable mechanism for dynamic multicomponent and functional biomolecular condensate mimics and for autonomous materials design in general.