Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

Capillary forces generated by biomolecular condensates

Nature volume 609, pages 255–264 (2022)Cite this article

Subjects

Abstract

Liquid–liquid phase separation and related phase transitions have emerged as generic mechanisms in living cells for the formation of membraneless compartments or biomolecular condensates. The surface between two immiscible phases has an interfacial tension, generating capillary forces that can perform work on the surrounding environment. Here we present the physical principles of capillarity, including examples of how capillary forces structure multiphase condensates and remodel biological substrates. As with other mechanisms of intracellular force generation, for example, molecular motors, capillary forces can influence biological processes. Identifying the biomolecular determinants of condensate capillarity represents an exciting frontier, bridging soft matter physics and cell biology.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Examples of capillarity in multiphase condensate organization.
Fig. 2: Capillarity on substrates.
Fig. 3: Capillary forces and genome organization.
Fig. 4: Surfactants.

Similar content being viewed by others

References

  1. Shin, Y. & Brangwynne, C. P. Liquid phase condensation in cell physiology and disease. Science 357, eaaf4382 (2017).

    Article  CAS  PubMed  Google Scholar 

  2. Banani, S. F., Lee, H. O., Hyman, A. A. & Rosen, M. K. Biomolecular condensates: organizers of cellular biochemistry. Nat. Rev. Mol. Cell Biol. 18, 285–298 (2017).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Brangwynne, C. P. et al. Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science 324, 1729–1732 (2009).

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Seydoux, G. The P granules of C. elegans: a genetic model for the study of RNA–protein condensates. J. Mol. Biol. 430, 4702–4710 (2018).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Feric, M. et al. Coexisting liquid phases underlie nucleolar subcompartments. Cell 165, 1686–1697 (2016). Nucleoli are multiphase liquid condensates whose core–shell organization is governed by relative interfacial tensions.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Frottin, F. et al. The nucleolus functions as a phase-separated protein quality control compartment. Science 365, 342–347 (2019).

    Article  ADS  CAS  PubMed  Google Scholar 

  7. Wheeler, J. R., Matheny, T., Jain, S., Abrisch, R. & Parker, R. Distinct stages in stress granule assembly and disassembly. eLife 5, e18413 (2016).

    Article  PubMed Central  PubMed  Google Scholar 

  8. Freeman Rosenzweig, E. S. et al. The eukaryotic CO2-concentrating organelle is liquid-like and exhibits dynamic reorganization. Cell 171, 148–162.e19 (2017).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Kilic, S. et al. Phase separation of 53BP1 determines liquid-like behavior of DNA repair compartments. EMBO J. 38, e101379 (2019).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Li, P. et al. Phase transitions in the assembly of multivalent signalling proteins. Nature 483, 336–340 (2012).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  11. Martin, E. W. et al. Valence and patterning of aromatic residues determine the phase behavior of prion-like domains. Science 367, 694–699 (2020).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  12. Zarzar, L. D. et al. Dynamically reconfigurable complex emulsions via tunable interfacial tensions. Nature 518, 520–524 (2015).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  13. Marthelot, J., Strong, E. F., Reis, P. M. & Brun, P.-T. Designing soft materials with interfacial instabilities in liquid films. Nat. Commun. 9, 4477 (2018).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  14. Duprat, C., Aristoff, J. M. & Stone, H. A. Dynamics of elastocapillary rise. J. Fluid Mech. 679, 641–654 (2011).

    Article  ADS  MATH  Google Scholar 

  15. Roman, B. & Bico, J. Elasto-capillarity: deforming an elastic structure with a liquid droplet. J. Phys. Condens. Matter 22, 493101 (2010).

    Article  CAS  PubMed  Google Scholar 

  16. Steinberg, M. S. Adhesion in development: an historical overview. Dev. Biol. 180, 377–388 (1996).

    Article  CAS  PubMed  Google Scholar 

  17. Hayashi, T. & Carthew, R. W. Surface mechanics mediate pattern formation in the developing retina. Nature 431, 647–652 (2004).

    Article  ADS  CAS  PubMed  Google Scholar 

  18. Rubinstein, M. & Colby, R. H. Polymer Physics (Oxford Univ. Press, 2003).

  19. Aarts, D. G. A. L., Schmidt, M. & Lekkerkerker, H. N. W. Direct visual observation of thermal capillary waves. Science 304, 847–850 (2004).

    Article  ADS  CAS  PubMed  Google Scholar 

  20. Dill, K. & Bromberg, S. Molecular Driving Forces: Statistical Thermodynamics in Biology, Chemistry, Physics, and Nanoscience (Garland Science, 2010).

  21. Mao, S., Kuldinow, D., Haataja, M. P. & Košmrlj, A. Phase behavior and morphology of multicomponent liquid mixtures. Soft Matter 15, 1297–1311 (2019).

    Article  ADS  CAS  PubMed  Google Scholar 

  22. Cahn, J. W. & Hilliard, J. E. Free energy of a nonuniform system. I. Interfacial free energy. J. Chem. Phys. 28, 258–267 (1958).

    Article  ADS  CAS  MATH  Google Scholar 

  23. Berry, J., Brangwynne, C. P. & Haataja, M. Physical principles of intracellular organization via active and passive phase transitions. Rep. Prog. Phys. 81, 046601 (2018).

    Article  ADS  CAS  PubMed  Google Scholar 

  24. Molliex, A. et al. Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization. Cell 163, 123–133 (2015).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Lin, Y., Protter, D. S. W., Rosen, M. K. & Parker, R. Formation and maturation of phase-separated liquid droplets by RNA-binding proteins. Mol. Cell 60, 208–219 (2015).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Zhang, H. et al. RNA controls polyQ protein phase transitions. Mol. Cell 60, 220–230 (2015).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Putnam, A., Cassani, M., Smith, J. & Seydoux, G. A gel phase promotes condensation of liquid P granules in Caenorhabditis elegans embryos. Nat. Struct. Mol. Biol. 26, 220–226 (2019).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Patel, A. et al. A liquid-to-solid phase transition of the ALS protein FUS accelerated by disease mutation. Cell 162, 1066–1077 (2015).

    Article  CAS  PubMed  Google Scholar 

  29. Eggers, J., Lister, J. R. & Stone, H. A. Coalescence of liquid drops. J. Fluid Mech. 401, 293–310 (1999).

    Article  ADS  MathSciNet  CAS  MATH  Google Scholar 

  30. Rosowski, K. A. et al. Elastic ripening and inhibition of liquid–liquid phase separation. Nat. Phys. 16, 422–425 (2020).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Sanders, D. W. et al. Competing protein–RNA interaction networks control multiphase intracellular organization. Cell 181, 306–324.e28 (2020).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Fei, J. et al. Quantitative analysis of multilayer organization of proteins and RNA in nuclear speckles at super resolution. J. Cell Sci. 130, 4180–4192 (2017).

    CAS  PubMed Central  PubMed  Google Scholar 

  33. Kaur, T. et al. Sequence-encoded and composition-dependent protein–RNA interactions control multiphasic condensate morphologies. Nat. Commun. 12, 872 (2021). A ternary system of protein and RNA is used to show that the wetting morphologies of the resulting biphasic condensates depend strongly on component stoichiometry and intermolecular interaction hierarchy.

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  34. Fisher, R. S. & Elbaum-Garfinkle, S. Tunable multiphase dynamics of arginine and lysine liquid condensates. Nat. Commun. 11, 4628 (2020).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  35. Boeynaems, S. et al. Spontaneous driving forces give rise to protein–RNA condensates with coexisting phases and complex material properties. Proc. Natl Acad. Sci. USA 116, 7889–7898 (2019).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Simon, J. R., Carroll, N. J., Rubinstein, M., Chilkoti, A. & López, G. P. Programming molecular self-assembly of intrinsically disordered proteins containing sequences of low complexity. Nat. Chem. 9, 509–515 (2017).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Gall, J. G., Bellini, M., Wu, Z. & Murphy, C. Assembly of the nuclear transcription and processing machinery: Cajal bodies (coiled bodies) and transcriptosomes. Mol. Biol. Cell 10, 4385–4402 (1999).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Pena, E., Berciano, M. T., Fernandez, R., Ojeda, J. L. & Lafarga, M. Neuronal body size correlates with the number of nucleoli and Cajal bodies, and with the organization of the splicing machinery in rat trigeminal ganglion neurons. J. Comp. Neurol. 430, 250–263 (2001).

    Article  CAS  PubMed  Google Scholar 

  39. Caragine, C. M., Haley, S. C. & Zidovska, A. Surface fluctuations and coalescence of nucleolar droplets in the human cell nucleus. Phys. Rev. Lett. 121, 148101 (2018).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  40. Ijavi, M. et al. Surface tensiometry of phase separated protein and polymer droplets by the sessile drop method. Soft Matter 17, 1655–1662 (2021).

    Article  ADS  CAS  PubMed  Google Scholar 

  41. Jawerth, L. M. et al. Salt-dependent rheology and surface tension of protein condensates using optical traps. Phys. Rev. Lett. 121, 258101 (2018).

    Article  ADS  CAS  PubMed  Google Scholar 

  42. Wang, H., Kelley, F. M., Milovanovic, D., Schuster, B. S. & Shi, Z. Surface tension and viscosity of protein condensates quantified by micropipette aspiration. Biophys. Rep. 1, 100011 (2021).

    CAS  Google Scholar 

  43. Bergeron-Sandoval, L.-P. et al. Endocytic proteins with prion-like domains form viscoelastic condensates that enable membrane remodeling. Proc. Natl Acad. Sci. USA 118, e2113789118 (2021).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Shin, Y. et al. Spatiotemporal control of intracellular phase transitions using light-activated optoDroplets. Cell 168, 159–171.e14 (2017).

    Article  CAS  PubMed  Google Scholar 

  45. Bracha, D. et al. Mapping local and global liquid phase behavior in living cells using photo-oligomerizable seeds. Cell 175, 1467–1480.e13 (2018).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Dine, E., Gil, A. A., Uribe, G., Brangwynne, C. P. & Toettcher, J. E. Protein phase separation provides long-term memory of transient spatial stimuli. Cell Syst. 6, 655–663.e5 (2018).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Shin, Y. et al. Liquid nuclear condensates mechanically sense and restructure the genome. Cell 175, 1481–1491.e13 (2018). Nuclear condensates exert capillary forces on targeted genomic loci to pull them together while excluding the rest of the neighbouring genome.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Narayanan, A. et al. A first order phase transition mechanism underlies protein aggregation in mammalian cells. eLife 8, e39695 (2019).

    Article  PubMed Central  PubMed  Google Scholar 

  49. Shimobayashi, S., Ronceray, P., Sanders, D. W., Haataja, M. & Brangwynne, C. P. Nucleation landscape of biomolecular condensates. Nature 599, 503–506 (2021).

    Article  ADS  CAS  PubMed  Google Scholar 

  50. Kashchiev, D. Nucleation (Elsevier, 2000).

  51. Wiegand, T. & Hyman, A. A. Drops and fibers—how biomolecular condensates and cytoskeletal filaments influence each other. Emerg. Top. Life Sci. 4, 247–261 (2020).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Su, X. et al. Phase separation of signaling molecules promotes T cell receptor signal transduction. Science 352, 595–599 (2016).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  53. Feric, M. & Brangwynne, C. P. A nuclear F-actin scaffold stabilizes ribonucleoprotein droplets against gravity in large cells. Nat. Cell Biol. 15, 1253–1259 (2013).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Böddeker, T. J. et al. Non-specific adhesive forces between filaments and membraneless organelles. Nat. Phys. 18, 571–578 (2022). Tubulin subunits and microtubules adhere to condensate interfaces in a manner consistent with a Pickering model that accounts for the finite interfacial thickness.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Sanchez, T., Chen, D. T. N., DeCamp, S. J., Heymann, M. & Dogic, Z. Spontaneous motion in hierarchically assembled active matter. Nature 491, 431–434 (2012).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  56. Kumar, N., Zhang, R., de Pablo, J. J. & Gardel, M. L. Tunable structure and dynamics of active liquid crystals. Sci. Adv. 4, eaat7779 (2018).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  57. Weirich, K. L. et al. Liquid behavior of cross-linked actin bundles. Proc. Natl Acad. Sci. USA 114, 2131–2136 (2017).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  58. Zwicker, D., Seyboldt, R., Weber, C. A., Hyman, A. A. & Jülicher, F. Growth and division of active droplets provides a model for protocells. Nat. Phys. 13, 408–413 (2017).

    Article  CAS  Google Scholar 

  59. Weirich, K. L., Dasbiswas, K., Witten, T. A., Vaikuntanathan, S. & Gardel, M. L. Self-organizing motors divide active liquid droplets. Proc. Natl Acad. Sci. USA 116, 11125–11130 (2019).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  60. Jiang, H. et al. Phase transition of spindle-associated protein regulate spindle apparatus assembly. Cell 163, 108–122 (2015).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. King, M. R. & Petry, S. Phase separation of TPX2 enhances and spatially coordinates microtubule nucleation. Nat. Commun. 11, 270 (2020).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  62. Hernández-Vega, A. et al. Local nucleation of microtubule bundles through tubulin concentration into a condensed tau phase. Cell Rep. 20, 2304–2312 (2017). Microtubules nucleate from tau condensates, resulting in a wetted network of microtubule bundles, the wettability of which can be tuned by heparin.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Siahaan, V. et al. Kinetically distinct phases of tau on microtubules regulate kinesin motors and severing enzymes. Nat. Cell Biol. 21, 1086–1092 (2019).

    Article  CAS  PubMed  Google Scholar 

  64. Jijumon, A. S. et al. Lysate-based pipeline to characterize microtubule-associated proteins uncovers unique microtubule behaviours. Nat. Cell Biol. 24, 253–267 (2022).

    Article  CAS  PubMed  Google Scholar 

  65. Setru, S. U. et al. A hydrodynamic instability drives protein droplet formation on microtubules to nucleate branches. Nat. Phys. 17, 493–498 (2021). A Rayleigh–Plateau instability with condensed TPX2 on microtubules results in droplets that serve as reaction hubs to form microtubule branches.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Petry, S., Groen, A. C., Ishihara, K., Mitchison, T. J. & Vale, R. D. Branching microtubule nucleation in Xenopus egg extracts mediated by augmin and TPX2. Cell 152, 768–777 (2013).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Valentine, M. T., Fordyce, P. M., Krzysiak, T. C., Gilbert, S. P. & Block, S. M. Individual dimers of the mitotic kinesin motor Eg5 step processively and support substantial loads in vitro. Nat. Cell Biol. 8, 470–476 (2006).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Bäuerlein, F. J. B. et al. In situ architecture and cellular interactions of polyQ inclusions. Cell 171, 179–187.e10 (2017).

    Article  CAS  PubMed  Google Scholar 

  69. Fisher, R. S., Jimenez, R. M., Soto, E., Kalev, D. & Elbaum-Garfinkle, S. An apparent core/shell architecture of polyQ aggregates in the aging Caenorhabditis elegans neuron. Protein Sci. 30, 1482–1486 (2021).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Yu, H. et al. HSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells. Science 371, eabb4309 (2021).

    Article  CAS  PubMed  Google Scholar 

  71. Updike, D. L., Hachey, S. J., Kreher, J. & Strome, S. P granules extend the nuclear pore complex environment in the C. elegans germ line. J. Cell Biol. 192, 939–948 (2011).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Yuan, F. et al. Membrane bending by protein phase separation. Proc. Natl Acad. Sci. USA 118, e2017435118 (2021).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. Kusumaatmaja, H. & Lipowsky, R. Droplet-induced budding transitions of membranes. Soft Matter 7, 6914–6919 (2011).

    Article  ADS  CAS  Google Scholar 

  74. Agudo-Canalejo, J. et al. Wetting regulates autophagy of phase-separated compartments and the cytosol. Nature 591, 142–146 (2021). Autophagosomes sequester p62-rich condensates by wrapping around them via a wetting interaction; successful autophagy depends on condensate size, interfacial tension and membrane stiffness.

    Article  ADS  CAS  PubMed  Google Scholar 

  75. Kusumaatmaja, H. et al. Wetting of phase-separated droplets on plant vacuole membranes leads to a competition between tonoplast budding and nanotube formation. Proc. Natl Acad. Sci. USA 118, e2024109118 (2021). Wetting of phase-separated droplets on plant vacuolar membranes can lead to membrane budding or the formation of membrane nanotubes depending on the contact angle and the membrane spontaneous curvature.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Feeney, M., Kittelmann, M., Menassa, R., Hawes, C. & Frigerio, L. Protein storage vacuoles originate from remodeled preexisting vacuoles in Arabidopsis thaliana. Plant Physiol. 177, 241–254 (2018).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Zheng, H. & Staehelin, L. A. Protein storage vacuoles are transformed into lytic vacuoles in root meristematic cells of germinating seedlings by multiple, cell type-specific mechanisms. Plant Physiol. 155, 2023–2035 (2011).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Dimova, R. & Lipowsky, R. Lipid membranes in contact with aqueous phases of polymer solutions. Soft Matter 8, 6409–6415 (2012).

    Article  ADS  CAS  Google Scholar 

  79. Wei, M.-T. et al. Nucleated transcriptional condensates amplify gene expression. Nat. Cell Biol. 22, 1187–1196 (2020).

    Article  CAS  PubMed  Google Scholar 

  80. Sabari, B. R. et al. Coactivator condensation at super-enhancers links phase separation and gene control. Science 361, eaar3958 (2018).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Gibson, B. A. et al. Organization of chromatin by intrinsic and regulated phase separation. Cell 179, 470–484.e21 (2019).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  82. Tatavosian, R. et al. Nuclear condensates of the Polycomb protein chromobox 2 (CBX2) assemble through phase separation. J. Biol. Chem. 294, 1451–1463 (2019).

    Article  CAS  PubMed  Google Scholar 

  83. Strom, A. R. et al. Phase separation drives heterochromatin domain formation. Nature 547, 241–245 (2017).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  84. Larson, A. G. et al. Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin. Nature 547, 236–240 (2017).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  85. Morin, J. A. et al. Sequence-dependent surface condensation of a pioneer transcription factor on DNA. Nat. Phys. 18, 271–276 (2022).

  86. Quail, T. et al. Force generation by protein–DNA co-condensation. Nat. Phys. 17, 1007–1012 (2021). The condensed transcription factor FoxA1 wets DNA and regulates its tension by allowing slack DNA to spool into FoxA1 droplets.

    Article  CAS  Google Scholar 

  87. Elettro, H., Neukirch, S., Vollrath, F. & Antkowiak, A. In-drop capillary spooling of spider capture thread inspires hybrid fibers with mixed solid–liquid mechanical properties. Proc. Natl Acad. Sci. USA 113, 6143–6147 (2016).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  88. Keenen, M. M. et al. HP1 proteins compact DNA into mechanically and positionally stable phase separated domains. eLife 10, e64563 (2021).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  89. Gao, Y., Han, M., Shang, S., Wang, H. & Qi, L. S. Interrogation of the dynamic properties of higher-order heterochromatin using CRISPR/dCas9. Mol. Cell 81, 4287–4299.e5 (2021).

    Article  CAS  PubMed  Google Scholar 

  90. Wang, H. et al. CRISPR-mediated programmable 3D genome positioning and nuclear organization. Cell 175, 1405–1417.e14 (2018).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  91. Jack, A. et al. Compartmentalization of telomeres through DNA-scaffolded phase separation. Dev. Cell 57, 277–290.e9 (2022).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  92. Lee, D. S. W., Wingreen, N. S. & Brangwynne, C. P. Chromatin mechanics dictates subdiffusion and coarsening dynamics of embedded condensates. Nat. Phys. 17, 531–538 (2021).

    Article  CAS  Google Scholar 

  93. Ronceray, P., Sheng, M., Košmrlj, A. & Haataja, M. P. Liquid demixing in elastic networks: cavitation, permeation, or size selection?. EPL 137, 67001 (2022).

    Article  ADS  Google Scholar 

  94. Zhang, Y., Lee, D. S. W., Meir, Y., Brangwynne, C. P. & Wingreen, N. S. Mechanical frustration of phase separation in the cell nucleus by chromatin. Phys. Rev. Lett. 126, 258102 (2021).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  95. Snead, W. T. et al. Membrane surfaces regulate assembly of ribonucleoprotein condensates. Nat. Cell Biol. 24, 461–470 (2022).

    Article  CAS  PubMed  Google Scholar 

  96. Cochard, A. et al. RNA at the surface of phase-separated condensates impacts their size and number. Biophys. J.121, 1675–1690 (2022).

  97. Boisvert, F. M., Hendzel, M. J. & Bazett-Jones, D. P. Promyelocytic leukemia (PML) nuclear bodies are protein structures that do not accumulate RNA. J. Cell Biol. 148, 283–292 (2000).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  98. Tauber, D. et al. Modulation of RNA condensation by the DEAD-box protein eIF4A. Cell 180, 411–426.e16 (2020).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  99. Hilbert, L. et al. Transcription organizes euchromatin via microphase separation. Nat. Commun. 12, 1360 (2021).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  100. Plys, A. J. et al. Phase separation of Polycomb-repressive complex 1 is governed by a charged disordered region of CBX2. Genes Dev. 33, 799–813 (2019).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  101. Falk, M. et al. Heterochromatin drives compartmentalization of inverted and conventional nuclei. Nature 570, 395–399 (2019).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  102. De, S., Malik, S., Ghosh, A., Saha, R. & Saha, B. A review on natural surfactants. RSC Adv. 5, 65757–65767 (2015).

    Article  ADS  CAS  Google Scholar 

  103. Cuylen, S. et al. Ki-67 acts as a biological surfactant to disperse mitotic chromosomes. Nature 535, 308–312 (2016).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  104. Cuylen-Haering, S. et al. Chromosome clustering by Ki-67 excludes cytoplasm during nuclear assembly. Nature 587, 285–290 (2020).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  105. Stenström, L. et al. Mapping the nucleolar proteome reveals a spatiotemporal organization related to intrinsic protein disorder. Mol. Syst. Biol. 16, e9469 (2020).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  106. Brangwynne, C. P., Mitchison, T. J. & Hyman, A. A. Active liquid-like behavior of nucleoli determines their size and shape in Xenopus laevis oocytes. Proc. Natl Acad. Sci. USA 108, 4334–4339 (2011).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  107. Elbaum-Garfinkle, S. et al. The disordered P granule protein LAF-1 drives phase separation into droplets with tunable viscosity and dynamics. Proc. Natl Acad. Sci. USA 112, 7189–7194 (2015).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  108. Kelley, F. M., Favetta, B., Regy, R. M., Mittal, J. & Schuster, B. S. Amphiphilic proteins coassemble into multiphasic condensates and act as biomolecular surfactants. Proc. Natl Acad. Sci. USA 118, e2109967118 (2021). Amphiphilic surfactant-like proteins regulate the size and multiphasic wetting morphologies of condensates in a concentration-dependent and sequence-dependent manner.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  109. Sanchez-Burgos, I., Joseph, J. A., Collepardo-Guevara, R. & Espinosa, J. R. Size conservation emerges spontaneously in biomolecular condensates formed by scaffolds and surfactant clients. Sci. Rep. 11, 15241 (2021).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  110. Subramaniam, A. B., Abkarian, M., Mahadevan, L. & Stone, H. A. Colloid science: non-spherical bubbles. Nature 438, 930 (2005).

    Article  ADS  CAS  PubMed  Google Scholar 

  111. Abkarian, M. et al. Dissolution arrest and stability of particle-covered bubbles. Phys. Rev. Lett. 99, 188301 (2007).

    Article  ADS  CAS  PubMed  Google Scholar 

  112. Dinsmore, A. D. et al. Colloidosomes: selectively permeable capsules composed of colloidal particles. Science 298, 1006–1009 (2002).

    Article  ADS  CAS  PubMed  Google Scholar 

  113. Binks, B. P. & Clint, J. H. Solid wettability from surface energy components: relevance to Pickering emulsions. Langmuir 18, 1270–1273 (2002).

    Article  CAS  Google Scholar 

  114. Folkmann, A. W., Putnam, A., Lee, C. F. & Putnam, G. Pickering stabilization of a dynamic intracellular emulsion. Science 373, 1218–1224 (2021). MEG-3 assemblies adhere to the interface of P granules and slow their coarsening through a Pickering effect, thereby stabilizing the emulsion of P granules.

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  115. Würger, A. Curvature-induced capillary interaction of spherical particles at a liquid interface. Phys. Rev. E 74, 041402 (2006).

    Article  ADS  MathSciNet  CAS  Google Scholar 

  116. Cavallaro, M. Jr, Botto, L., Lewandowski, E. P., Wang, M. & Stebe, K. J. Curvature-driven capillary migration and assembly of rod-like particles. Proc. Natl Acad. Sci. USA 108, 20923–20928 (2011).

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  117. Boruvka, L. & Neumann, A. W. Generalization of the classical theory of capillarity. J. Chem. Phys. 66, 5464–5476 (1977).

    Article  ADS  CAS  Google Scholar 

Download references

Acknowledgements

We thank members of our laboratories for helpful discussions; and M. Haataja for helpful comments on the manuscript. We acknowledge support from the Howard Hughes Medical Institute, the Princeton Biomolecular Condensate Program, and grants from the Princeton Center for Complex Materials, a MRSEC (NSF DMR-2011750), and the AFOSR MURI ‘Uncovering and applying the interfacial design principles of multiphasic natural and synthetic organelles’ (FA9550-20-1-0241). B.G. acknowledges the PD Soros Foundation. Both B.G. and Y.K. are supported by the NSF GRFP (DGE-2039656).

Author information

Author notes

  1. These authors contributed equally: Bernardo Gouveia, Yoonji Kim

Authors and Affiliations

  1. Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, USA

    Bernardo Gouveia & Clifford P. Brangwynne

  2. Department of Molecular Biology, Princeton University, Princeton, NJ, USA

    Yoonji Kim & Sabine Petry

  3. Department of Physics, Princeton University, Princeton, NJ, USA

    Joshua W. Shaevitz

  4. Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ, USA

    Howard A. Stone

  5. The Howard Hughes Medical Institute, Princeton, NJ, USA

    Clifford P. Brangwynne

Authors
  1. Bernardo Gouveia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoonji Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joshua W. Shaevitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sabine Petry
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Howard A. Stone
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Clifford P. Brangwynne
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

B.G., Y.K., H.A.S. and C.P.B. wrote the manuscript with input from J.W.S. and S.P. All authors contributed to conceptualization, design and editing of the manuscript.

Corresponding authors

Correspondence to Howard A. Stone or Clifford P. Brangwynne.

Ethics declarations

Competing interests

C.P.B. is a founder of and consultant for Nereid Therapeutics. All other authors declare no competing interests.

Peer review

Peer review information

Nature thanks the anonymous reviewers for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gouveia, B., Kim, Y., Shaevitz, J.W. et al. Capillary forces generated by biomolecular condensates. Nature 609, 255–264 (2022). https://doi.org/10.1038/s41586-022-05138-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41586-022-05138-6

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing