Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K.
Cavendish Laboratory, University of Cambridge, J J Thomson Avenue, Cambridge CB3 0HE, U.K.
Nano Lett. 2022 Jan 26;22(2):612-621. doi: 10.1021/acs.nanolett.1c03138. Epub 2022 Jan 10.
Liquid-liquid phase separation underlies the formation of biological condensates. Physically, such systems are microemulsions that in general have a propensity to fuse and coalesce; however, many condensates persist as independent droplets in the test tube and inside cells. This stability is crucial for their function, but the physicochemical mechanisms that control the emulsion stability of condensates remain poorly understood. Here, by combining single-condensate zeta potential measurements, optical microscopy, tweezer experiments, and multiscale molecular modeling, we investigate how the nanoscale forces that sustain condensates impact their stability against fusion. By comparing peptide-RNA (PR:PolyU) and proteinaceous (FUS) condensates, we show that a higher condensate surface charge correlates with a lower fusion propensity. Moreover, measurements of single condensate zeta potentials reveal that such systems can constitute classically stable emulsions. Taken together, these results highlight the role of passive stabilization mechanisms in protecting biomolecular condensates against coalescence.
液-液相分离是生物凝聚体形成的基础。从物理上讲，这样的系统是微乳液，通常有融合和聚结的倾向；然而，许多凝聚体在试管和细胞内仍然以独立的液滴形式存在。这种稳定性对它们的功能至关重要，但控制凝聚体乳液稳定性的物理化学机制仍知之甚少。在这里，我们通过结合单个凝聚体zeta 电位测量、光学显微镜、镊子实验和多尺度分子建模，研究了维持凝聚体的纳米尺度力如何影响它们对抗融合的稳定性。通过比较肽-RNA（PR:PolyU）和蛋白质（FUS）凝聚体，我们表明更高的凝聚体表面电荷与更低的融合倾向相关。此外，对单个凝聚体 zeta 电位的测量表明，此类系统可以构成经典稳定的乳液。总之，这些结果强调了被动稳定机制在保护生物分子凝聚体免受聚结方面的作用。
