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bioRxiv · 10.64898/2026.01.29.702704

Dual Effect of RNA-like Polyelectrolytes on Stability and Dynamics of Biomolecular Condensates: A Tale of Competitive Short and Long-range Interactions

Sharma, D.·Roy, S.·HAZRA, M. K.
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Abstract

Heterotypic biomolecular condensates underpin the spatiotemporal organization of cellular components and enable precise biological regulation. These condensates frequently comprise proteins and RNA at variable stoichiometries, with RNA acting as a key modulator through its ability to engage in both long-range electrostatic and short-range specific interactions. How such RNA-like components regulate condensate stability and dynamics across distinct interaction regimes, however, remains unclear. Here, we examine the role of RNA-like polyelectrolytes in tuning the stability and material properties of heterotypic condensates formed by designed short peptide sequences spanning a continuum from long-range electrostatics-to short-range hydrophobic interactions. By systematically strengthening short-range hydrophobic interactions while varying polyelectrolyte composition, we uncover a dual, regime-dependent role of RNA-like species. In electrostatics-dominated condensates, excessive polyelectrolyte concentration rapidly destabilizes droplets due to enhanced long-range repulsive interactions while the droplets retain stability until intermediate polyelectrolyte concentration fairly well. In contrast, in strongly hydrophobic condensates, polyelectrolytes function as multivalent sticker hubs, stabilizing condensates through favourable peptide- polyelectrolyte interactions. Polyelectrolyte enrichment within condensates is nonlinear with respect to mixing fraction and saturates at largest cluster mole fractions of [~]0.2-0.25. Condensate dynamics reflect this interplay: polyelectrolyte diffusivity is 20-40% higher in electrostatics dominated systems than in hydrophobic ones, while in extremely hydrophobic condensates, polyelectrolytes diffuse [~]50% more slowly than peptides, indicative of scaffold-like behaviour. Together, these results reveal tuneable and opposing roles of RNA-like polyelectrolytes in shaping condensate stability, dynamics, and morphology across diverse interaction regimes.

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Sharma, D., Roy, S., HAZRA, M. K.. 2026-01-30. Dual Effect of RNA-like Polyelectrolytes on Stability and Dynamics of Biomolecular Condensates: A Tale of Competitive Short and Long-range Interactions. https://doi.org/10.64898/2026.01.29.702704

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