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PreprintCited by 168RNA Research and SplicingElectrostatics and Colloid InteractionsSurfactants and Colloidal Systems

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Surface electrostatics govern the emulsion stability of biomolecular condensates

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Welsh, Timothy J., Krainer, Georg, Espinosa, Jorge R., Joseph, Jerelle A., Sridhar, Akshay, Jahnel, Marcus, Arter, William E., Saar, Kadi L., Alberti, Simon, Collepardo-Guevara, Rosana, Knowles, Tuomas P.J.·2020·Nano Letters
DOI 10.1101/2020.04.20.047910
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Abstract

Liquid–liquid phase separation underlies the formation of biological condensates. Physically, such systems are microemulsions which have a general propensity to fuse and coalesce; however, many condensates persist as independent droplets inside cells. This stability is crucial for their functioning, 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 modelling, we investigate how the forces that sustain condensates impact their stability against fusion. By comparing PR 25 :PolyU and FUS condensates, we show that a higher condensate surface charge correlates with a lower fusion propensity, and that this behavior can be inferred from their zeta potentials. We reveal that overall stabilization against fusion stems from a combination of repulsive forces between condensates and the effects that surface electrostatics have on lowering surface tension, thus shedding light on the molecular determinants of condensate coalescence.

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  • With many protein condensates carrying a small net surface charge, the transfer becomes even more restricted, either because of electrostatic attraction at the source droplet, or repulsion at the target droplet.

    “Moreover, with many protein condensates carrying a small net surface charge31, the transfer becomes even more restricted, either because of electrostatic attraction at the source droplet, or repulsion at the target droplet.”

    From Active coacervate droplets are protocells that grow and resist Ostwald ripening (2021) · cites this paper as [31]

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Research works printed but not linked: 111

  1. 10.1038/nature10879 · DOI
  2. 10.1126/science.aaw8653 · DOI · Paper page
  3. 10.1016/j.cell.2018.12.035 · DOI · Paper page
  4. 10.1016/j.tcb.2018.02.004 · DOI
  5. 10.1146/annurev-cellbio-100913-013325 · DOI · Paper page
  6. 10.1103/PhysRevLett.111.088101 · DOI
  7. 2018, Tuned Response, Cell, 168, 1028
  8. 10.1016/j.cell.2016.04.047 · DOI
  9. 10.1126/science.1172046 · DOI
  10. 10.1016/j.cell.2015.07.047 · DOI
  11. 2018, Quality Control of Membraneless Organelles, J. Mol. Biol., 430, 4711, 10.1016/j.jmb.2018.05.013 · DOI
  12. 10.1002/bies.201600042 · DOI
  13. 10.1126/science.aao5654 · DOI
  14. 10.1016/j.cell.2018.06.006 · DOI
  15. 10.1101/2020.05.04.076299 · DOI
  16. 10.1073/pnas.1504822112 · DOI · Paper page
  17. 10.7554/eLife.18413 · DOI
  18. 2018, Chemical-Reaction-Controlled Phase Separated Drops: Formation, Size Selection, and Coarsening, Phys. Rev. Lett., 120, 078102, 10.1103/PhysRevLett.120.078102 · DOI · Paper page
  19. 10.1126/science.aad9964 · DOI
  20. 10.1038/ncb2830 · DOI
  21. 2019, Physics of active emulsions, Reports Prog. Phys., 82, 064601, 10.1088/1361-6633/ab052b · DOI
  22. 10.1016/j.cell.2015.09.015 · DOI
  23. 2018, Physical principles of intracellular organization via active and passive phase transitions, Reports Prog. Phys., 81, 046601, 10.1088/1361-6633/aaa61e · DOI
  24. 1999, Zeta potential, effective diameter and multimodal size distribution in oil/water emulsion, Colloids Surfaces A Physicochem. Eng. Asp., 159, 253, 10.1016/S0927-7757(99)00281-2 · DOI
  25. 1988, Demulsification rate and zeta potential of O/W emulsions, Colloid Polym. Sci., 266, 937, 10.1007/BF01410850 · DOI
  26. 1992, Measurement and application of zeta-potential, Rud. Zb., 4, 147
  27. 2005, Random centroid optimization of phosphatidylglycerol stabilized lutein-enriched oil-in-water emulsions at acidic pH, Food Chem., 92, 737, 10.1016/j.foodchem.2004.12.029 · DOI
  28. 10.1101/603803 · DOI
  29. 10.1007/s00396-014-3276-y · DOI
  30. 2018, Effects of HLB value on oil-in-water emulsions: Droplet size, rheological behavior, zeta-potential, and creaming index, J. Ind. Eng. Chem., 67, 123, 10.1016/j.jiec.2018.06.022 · DOI
  31. 2018, On-chip label-free protein analysis with downstream electrodes for direct removal of electrolysis products, Lab Chip, 18, 162, 10.1039/C7LC00797C · DOI
  32. 2018, Enhancing the Resolution of Micro Free Flow Electrophoresis through Spatially Controlled Sample Injection, Anal. Chem., 90, 8998, 10.1021/acs.analchem.8b01205 · DOI
  33. 2018, Combining Affinity Selection and Specific Ion Mobility for Microchip Protein Sensing, Anal. Chem., 90, 10302, 10.1021/acs.analchem.8b02051 · DOI
  34. 10.3389/fnmol.2017.00264 · DOI
  35. 10.1016/j.molcel.2017.02.013 · DOI
  36. 10.1074/jbc.274.48.34337 · DOI
  37. 10.1038/srep13416 · DOI
  38. 2017, The FUS protein: Physiological functions and a role in amyotrophic lateral sclerosis, Mol. Biol., 51, 341, 10.1134/S0026893317020091 · DOI
  39. 10.1038/s41594-019-0250-x · DOI · Paper page
  40. 1957, Phase separation in polyelectrolyte solutions; theory of complex coacervation, J Cell Physiol Suppl, 49, 7, 10.1002/jcp.1030490404 · DOI
  41. 10.1371/journal.pcbi.1005941 · DOI
  42. S. Das , Y.-H. Lin , R. M. Vernon , J. D. Forman-Kay , H. S. Chan , arXiv, in press (available at http://arxiv.org/abs/2005.06712). · arXiv
  43. 10.1063/1.2183308 · DOI
  44. 1977, Triple-point coexistence properties of the lennard-jones system, Chem. Phys. Lett., 51, 155, 10.1016/0009-2614(77)85375-X · DOI
  45. 2013, On fluid-solid direct coexistence simulations: The pseudo-hard sphere model, J. Chem. Phys., 139, 144502, 10.1063/1.4823499 · DOI
  46. 2019, A unified mechanism for LLPS of ALS/FTLD-causing FUS as well as its modulation by ATP and oligonucleic acids, PLOS Biol., 17, e3000327, 10.1371/journal.pbio.3000327 · DOI
  47. 10.1371/journal.pbio.1000614 · DOI
  48. 10.1016/j.cell.2018.03.056 · DOI
  49. 10.1073/pnas.1917569117 · DOI
  50. 10.1093/nar/gkw081 · DOI
  51. 1981, The role of capillary wave fluctuations in determining the liquid-vapour interface analysis of the van der waals model, Mol. Phys., 42, 1169, 10.1080/00268978100100881 · DOI
  52. 2014, Computer simulation study of surface wave dynamics at the crystal-melt interface, J. Chem. Phys., 141, 034701, 10.1063/1.4886806 · DOI
  53. 10.1063/1.1747247 · DOI
  54. 2006, Thermodynamic expressions for the Tolman length, J. Chem. Phys., 124, 074701, 10.1063/1.2167642 · DOI
  55. 2014, A study of the ice-water interface using the TIP4P/2005 water model, Phys. Chem. Chem. Phys., 16, 22159, 10.1039/C4CP03398A · DOI
  56. G. Urbina-Villalba , N. Garcia-Valera , K. Rahn-Chique , Theoretical Prediction and experimental measurement of the mixed flocculation/coalescence rate of ionic Hexadecane-in-water nano-emulsions. arXiv (2015) (available at https://arxiv.org/abs/1507.01116). · arXiv
  57. 2018, Salt-Dependent Rheology and Surface Tension of Protein Condensates Using Optical Traps, Phys. Rev. Lett., 121, 258101, 10.1103/PhysRevLett.121.258101 · DOI
  58. 2015, Suppression of Ostwald ripening in active emulsions, Phys. Rev. E - Stat. Nonlinear, Soft Matter Phys., 92, 012317, 10.1103/PhysRevE.92.012317 · DOI · Paper page
  59. 10.1016/j.molcel.2019.03.019 · DOI
  60. 2002, Capillary mechanisms in membrane emulsification: oil-in-water emulsions stabilized by Tween 20 and milk proteins, Colloids Surfaces A Physicochem. Eng. Asp., 209, 83, 10.1016/S0927-7757(02)00167-X · DOI
  61. 10.1074/jbc.RA118.007222 · DOI
  62. 10.1016/j.molcel.2015.08.018 · DOI
  63. 2019, Spatial control of irreversible protein aggregation, Elife, 8, e42315, 10.7554/eLife.42315 · DOI
  64. 10.1016/j.tibs.2017.11.005 · DOI
  65. 10.1016/j.brainres.2018.04.036 · DOI
  66. 2019, Understanding Ostwald Ripening and Surface Charging Effects in Solvothermally-Prepared Metal Oxide–Carbon Anodes for High Performance Rechargeable Batteries, Adv. Energy Mater., 9, 1902194, 10.1002/aenm.201902194 · DOI
  67. 10.1038/s41467-019-11241-6 · DOI
  68. 2016, Hierarchical Size Scaling during Multicellular Growth and Development, Cell Rep., 17, 345, 10.1016/j.celrep.2016.09.007 · DOI
  69. 10.1002/(SICI)1096-9896(200006)191:2<181::AID-PATH607>3.0.CO;2-V · DOI
  70. 2017, Local Nucleation of Microtubule Bundles through Tubulin Concentration into a Condensed Tau Phase, Cell Rep., 20, 2304, 10.1016/j.celrep.2017.08.042 · DOI · Paper page
  71. 10.1002/jcc.20290 · DOI · Paper page
  72. 10.1021/ct700324x · DOI
  73. 10.1371/journal.pcbi.1000803 · DOI
  74. 10.1021/ct400617g · DOI
  75. 2018, On-chip label-free protein analysis with downstream electrodes for direct removal of electrolysis products, Lab Chip, 18, 162, 10.1039/C7LC00797C · DOI
  76. 2018, Combining Affinity Selection and Specific Ion Mobility for Microchip Protein Sensing, Anal. Chem., 90, 10302, 10.1021/acs.analchem.8b02051 · DOI
  77. 2018, Enhancing the Resolution of Micro Free Flow Electrophoresis through Spatially Controlled Sample Injection, Anal. Chem., 90, 8998, 10.1021/acs.analchem.8b01205 · DOI
  78. 2013, Integration and characterization of solid wall electrodes in microfluidic devices fabricated in a single photolithography step, Appl. Phys. Lett., 102, 184102, 10.1063/1.4803917 · DOI
  79. 10.1146/annurev.matsci.28.1.153 · DOI
  80. 2017, Microfluidic devices fabricated using fast wafer-scale LED-lithography patterning, Biomicrofluidics, 11, 014113, 10.1063/1.4976690 · DOI
  81. 10.1063/1.3466882 · DOI
  82. 10.1016/j.ymeth.2016.09.016 · DOI
  83. 2012, A simpler expression for Henry’s function describing the electrophoretic mobility of spherical colloids, J. Colloid Interface Sci., 388, 92, 10.1016/j.jcis.2012.08.026 · DOI
  84. 1956, Dielectric constant of water from 0 to 100 C, J. Res. Natl. Bur. Stand. (1934)., 56, 2641
  85. 1978, Viscosity of liquid water in the range −8°C to 150°C, J. Phys. Chem. Ref. Data, 7, 941, 10.1063/1.555581 · DOI · Paper page
  86. 10.1371/journal.pcbi.1005941 · DOI
  87. S. Das , Y.-H. Lin , R. M. Vernon , J. D. Forman-Kay , H. S. Chan , arXiv, in press (available at http://arxiv.org/abs/2005.06712). · arXiv
  88. 2014, A simple atomic-level hydrophobicity scale reveals protein interfacial structure, J. Mol. Biol., 426, 484, 10.1016/j.jmb.2013.09.039 · DOI
  89. J. S. Rowlinson and B. Widom , Molecular Theory of Capillarity (Clarendon Press, Oxford, 1982).
  90. 1995, Fast parallel algorithms for short-range molecular dynamics, J. Comput. Phys., 117, 1, 10.1006/jcph.1995.1039 · DOI · Paper page
  91. 10.1063/1.1747247 · DOI
  92. 2019, Breakdown of the law of rectilinear diameter and related surprises in the liquid-vapor coexistence in systems of patchy particles, J. Chem. Phys., 150, 224510, 10.1063/1.5098551 · DOI
  93. 10.1002/jcc.20290 · DOI · Paper page
  94. 10.1021/ct700324x · DOI
  95. 10.1371/journal.pcbi.1000803 · DOI
  96. 2015, Martini Coarse-Grained Force Field: Extension to DNA, J. Chem. Theory Comput., 11, 3932, 10.1021/acs.jctc.5b00286 · DOI
  97. 10.1021/ct400617g · DOI
  98. 2015, Gromacs: High performance molecular simulations through multi-level parallelism from laptops to supercomputers, SoftwareX, 1–2, 19
  99. 10.1038/nmeth.4067 · DOI
  100. 10.1063/1.466711 · DOI
  101. 10.1021/jz900079w · DOI
  102. 2013, Simulations of anionic lipid membranes: Development of interaction-specific ion parameters and validation using NMR data, J. Phys. Chem. B, 123, 9066
  103. 2011, Optimization of the CHARMM Additive Force Field for DNA: Improved Treatment of the BI/BII Conformational Equilibrium, J. Chem. Theory Comput., 8, 348
  104. 10.1002/jcc.21777 · DOI
  105. 10.1002/jcc.540130805 · DOI
  106. 10.1063/1.2408420 · DOI
  107. 10.1063/1.328693 · DOI
  108. 10.1063/1.470117 · DOI
  109. 10.1002/jcc.21787 · DOI
  110. 10.1016/0263-7855(96)00018-5 · DOI · Paper page
  111. 10.1088/0965-0393/18/1/015012 · DOI

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Metadata

Authors
Welsh, T. J., Krainer, G., Espinosa, J. R., Joseph, J. A., Sridhar, A., Jahnel, M., Arter, W. E., Saar, K. L., Alberti, S., Collepardo-Guevara, R., & Knowles, T. P. J.
Affiliations
  • University of Cambridge (GB)
  • Max Planck Institute of Molecular Cell Biology and Genetics (DE)
  • Biotechnologisches Zentrum (DE)
Corresponding author
  • Alberti, Simon
  • Knowles, Tuomas P.J.
ORCID
Venue
Nano Letters
Publisher
openRxiv
Published
2020-04-21
Volume
22
Issue
2
Pages
612-621
ISSN
1530-6984 (ISSN-L)
DOI
10.1101/2020.04.20.047910
OpenAlex
W3018725402
Cited by
168
References
0
Citations by year
2026: 29 · 2025: 46 · 2024: 38 · 2023: 23 · 2022: 15 · 2021: 13 · 2020: 4
FWCI
8.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Nano Letters (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Apollo (University of Cambridge) (submittedVersion)
  • Apollo
Funders
  • Winston Churchill Foundation of the United States
  • University of Cambridge (EP/P020259/1)
  • King's College London (EP/P020259/1)
  • European Commission (2007–2013, FP7 2007-2013, 841466, HORIZON2020, 766972, FP7/2007, 337969)
  • Directorate for Biological Sciences
  • Horizon 2020 Framework Programme (FP7/2007-2013, 803326, 841466, 766972)
  • Engineering and Physical Sciences Research Council (EP/P020259/1, EP/P020259, FP7/2007–2013)
  • Biotechnology and Biological Sciences Research Council
  • H2020 European Research Council (803326)
  • H2020 Future and Emerging Technologies (766972)
  • H2020 Marie Skłodowska-Curie Actions (841466)
  • FP7 Ideas: European Research Council (337969)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Electrostatics and Colloid Interactions
  • Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Surfactants and Colloidal Systems
Keywords
biomolecular condensates, emulsion stability, liquid-liquid phase separation, surface charge, zeta potential, surface electrostatics, surface tension, FUS, microemulsions
MeSH terms
Biomolecular Condensates, Emulsions, Proteins, RNA, Static Electricity

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