Surface Electrostatics Govern the Emulsion Stability\nof Biomolecular Condensates
Timothy J. Welsh, Georg Krainer, Jorge R. Espinosa, Jerelle A. Joseph, Akshay Sridhar, Marcus Jahnel, William E. Arter, Kadi L. Saar, Simon Alberti, Rosana Collepardo‐Guevara, Tuomas P. J. Knowles
Abstract
Liquid–liquid\nphase separation underlies the formation of\nbiological condensates. Physically, such systems are microemulsions\nthat in general have a propensity to fuse and coalesce; however, many\ncondensates persist as independent droplets in the test tube and inside\ncells. This stability is crucial for their function, but the physicochemical\nmechanisms that control the emulsion stability of condensates remain\npoorly understood. Here, by combining single-condensate zeta potential\nmeasurements, optical microscopy, tweezer experiments, and multiscale\nmolecular modeling, we investigate how the nanoscale forces that sustain\ncondensates impact their stability against fusion. By comparing peptide–RNA\n(PR<sub>25</sub>:PolyU) and proteinaceous (FUS) condensates, we show\nthat a higher condensate surface charge correlates with a lower fusion\npropensity. Moreover, measurements of single condensate zeta potentials\nreveal that such systems can constitute classically stable emulsions.\nTaken together, these results highlight the role of passive stabilization\nmechanisms in protecting biomolecular condensates against coalescence.