Sequence-encoded intermolecular base pairing modulates fluidity in DNA and RNA condensates.

Nature uses bottom-up self-assembly to build structures with remarkable complexity and functionality. Understanding how molecular-scale interactions translate to macroscopic properties remains a major challenge and requires systems that effectively bridge these two scales. Here, we generate DNA and RNA-based liquids with exquisite programmability in their macroscopic rheological properties. In the presence of multivalent cations, nucleic acids can condense to a liquid-like state. Within these liquids, DNA and RNA retain sequence-specific hybridization abilities. We show that sequence-specific inter-molecular hybridization in the condensed phase cross-links molecules and slows down chain dynamics. This reduced chain mobility is mirrored in the macroscopic properties of the condensates. Molecular diffusivity and material viscosity scale with the inter-molecular hybridization energy, enabling precise sequence-based modulation of condensate properties over several orders of magnitude. Our work offers a robust platform to create bottom-up programmable fluids and may help advance our understanding of liquid-like compartments in cells.