Origin of Viscoelasticity in Protein-RNA Condensates

Biomolecular condensates are biopolymer-rich liquid-like droplets that regulate cellular biochemistry and constitute a prevalent mode for intracellular organization. These condensates are thought to form via liquid-liquid phase separation of cellular proteins and nucleic acids. It has been suggested that many intracellular protein-RNA condensates are complex viscoelastic fluids, albeit the molecular driving forces that control their viscoelasticity remain to be elucidated. Here, we perform quantitative rheological characterization of protein-RNA condensates using active and passive optical tweezer-based microrheology. We find that protein-RNA condensates are viscoelastic fluids with time-dependent viscous and elastic moduli that resemble a typical Maxwell fluid. By mapping the viscoelastic behavior of condensates formed by a series of designed protein sequences, we reveal simple analytics that describe how the amino-acid sequence composition and patterning encode the viscoelastic behavior of protein-RNA condensates. Overall, our findings shed light on the molecular determinants of viscoelasticity in protein-RNA condensates and provide guiding principles for designing artificial protein-RNA condensates with programmable viscoelastic behavior.