Journal
NANO LETTERS
Volume 22, Issue 2, Pages 612-621Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.1c03138
Keywords
Liquid-liquid phase separation; microfluidics; zeta potential; colloid stability; FUS
Categories
Funding
- European Research Council (ERC) under the European Union's Seventh Framework Programme (FP7/2007-2013) through the ERC grant PhysProt [337969]
- European Research Council (ERC) under the European Union's Horizon 2020 Framework Programme through the Future and Emerging Technologies (FET) grant NanoPhlow [766972]
- European Research Council (ERC) under the European Union's Horizon 2020 Framework Programme through the Marie Sklodowska-Curie grant MicroSPARK [841466]
- European Research Council (ERC) under the under the European Union's Horizon 2020 research and innovation programme through the ERC grant InsideChromatin [803326]
- University of Cambridge
- Wolfson College Junior Research Fellowship
- Winston Churchill Foundation of the United States
- Harding Distinguished Postgraduate Scholar Programme
- Winton Advanced Research Fellowship
- Oppenheimer Research Fellowship
- Roger Ekins Fellowship
- King's College Research Fellowship
- Engineering and Physical Sciences Research Council
- Schmidt Science Fellowship
- Rhodes Trust
- EPSRC [EP/P020259/1.]
- Marie Curie Actions (MSCA) [841466] Funding Source: Marie Curie Actions (MSCA)
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In this study, the impact of nanoscale forces on the stability of biomolecular condensates is investigated. It is found that condensates with higher surface charge have a lower propensity for fusion, highlighting the role of passive stabilization mechanisms in protecting biomolecular condensates against coalescence.
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 (PR25: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.
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