Surface Electrostatics Govern the Emulsion Stability of Biomolecular Condensates

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Timothy J Welsh - , University of Cambridge (Author)
  • Georg Krainer - , University of Cambridge (Author)
  • Jorge R Espinosa - , University of Cambridge (Author)
  • Jerelle A Joseph - , University of Cambridge (Author)
  • Akshay Sridhar - , University of Cambridge (Author)
  • Marcus Jahnel - , Dynamics of Biomolecules (Research Group) (Author)
  • William E Arter - , University of Cambridge (Author)
  • Kadi L Saar - , University of Cambridge (Author)
  • Simon Alberti - , Chair of Cellular Biochemistry (Author)
  • Rosana Collepardo-Guevara - , University of Cambridge (Author)
  • Tuomas P J Knowles - , University of Cambridge (Author)

Abstract

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.

Details

Original languageEnglish
Pages (from-to)612-621
Number of pages10
JournalNano letters
Volume22
Issue number2
Publication statusPublished - 10 Jan 2022
Peer-reviewedYes

External IDs

Scopus 85123385700
WOS 000745242500001
Mendeley de0c9c6c-7fd4-3408-ad0a-326babfb1262
ORCID /0000-0003-4017-6505/work/142253795

Keywords

Research priority areas of TU Dresden

DFG Classification of Subject Areas according to Review Boards

Keywords

  • Biomolecular Condensates, Emulsions, Proteins/chemistry, RNA/chemistry, Static Electricity, FUS, zeta potential, Liquid-liquid phase separation, colloid stability, microfluidics, Liquid−liquid phase separation, Fus, Zeta potential, Colloid stability, Microfluidics