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Surface phase separation in a confined space

Daoning Wu1 and Jie Lin2,3,*

  • *Contact author: linjie@pku.edu.cn
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Phys. Rev. Research 8, 033007 – Published 6 July, 2026

DOI: https://doi.org/10.1103/qyx1-nv48

Abstract

Biomolecular condensates frequently form near surfaces, including lipid membranes. However, the effect of a surface on phase separation within a cell, a confined system, remains elusive. In this work, we study surface phase separation under the constraint of a finite number of molecules in a confined space and identify three wetting states: thin, intermediate, and thick. Notably, the intermediate state, which is unstable in a fixed-chemical-potential system, can be stabilized in confinement below a critical width. Intriguingly, in wider systems, the intermediate solution becomes unstable due to a negative relationship between the chemical potential and particle number, leading to partial-wetting or prewetting droplets. Importantly, as the particle volume fraction increases from a lower value starting from a homogeneous surface, droplets form when the average volume fraction reaches the threshold of the intermediate state, which can be much lower than the threshold of bulk spinodal decomposition. Our theory elucidates the kinetic pathways of droplet formation in a confined system, providing crucial insights into how biomolecular condensates near surfaces respond to cellular events, such as the synthesis of biomolecules.

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References (40)

  1. C. P. Brangwynne, C. R. Eckmann, D. S. Courson, A. Rybarska, C. Hoege, J. Gharakhani, F. Jülicher, and A. A. Hyman, Germline P granules are liquid droplets that localize by controlled dissolution/condensation, Science 324, 1729 (2009).
  2. P. Li, S. Banjade, H.-C. Cheng, S. Kim, B. Chen, L. Guo, M. Llaguno, J. V. Hollingsworth, D. S. King, S. F. Banani, et al., Phase transitions in the assembly of multivalent signalling proteins, Nature (London) 483, 336 (2012).
  3. S. F. Banani, H. O. Lee, A. A. Hyman, and M. K. Rosen, Biomolecular condensates: Organizers of cellular biochemistry, Nat. Rev. Mol. Cell Biol. 18, 285 (2017).
  4. J. Berry, C. P. Brangwynne, and M. Haataja, Physical principles of intracellular organization via active and passive phase transitions, Rep. Prog. Phys. 81, 046601 (2018).
  5. S. Alberti and A. A. Hyman, Biomolecular condensates at the nexus of cellular stress, protein aggregation disease and ageing, Nat. Rev. Mol. Cell Biol. 22, 196 (2021).
  6. A. W. Fritsch, A. F. Diaz-Delgadillo, O. Adame-Arana, C. Hoege, M. Mittasch, M. Kreysing, M. Leaver, A. A. Hyman, F. Jülicher, and C. A. Weber, Local thermodynamics govern formation and dissolution of Caenorhabditis elegans P granule condensates, Proc. Natl. Acad. Sci. USA 118, e2102772118 (2021).
  7. F. Jülicher and C. A. Weber, Droplet physics and intracellular phase separation, Annu. Rev. Condens. Matter Phys. 15, 237 (2024).
  8. L. Meng, S. Mao, and J. Lin, Heterogeneous elasticity drives ripening and controls bursting kinetics of transcriptional condensates, Proc. Natl. Acad. Sci. USA 121, e2316610121 (2024).
  9. G. Pei, H. Lyons, P. Li, and B. R. Sabari, Transcription regulation by biomolecular condensates, Nat. Rev. Mol. Cell Biol. 26, 213 (2025).
  10. Y. Wu, X. Wang, L. Meng, Z. Liao, W. Ji, P. Zhang, J. Lin, and Q. Guo, Translation landscape of stress granules, Sci. Adv. 11, eady6859 (2025).
  11. W. T. Snead and A. S. Gladfelter, The control centers of biomolecular phase separation: How membrane surfaces, PTMs, and active processes regulate condensation, Mol. Cell 76, 295 (2019).
  12. A. Mangiarotti and R. Dimova, Biomolecular condensates in contact with membranes, Annu. Rev. Biophys. 53, 319 (2024).
  13. P. Lalchand, D.-D. Ashley, and X. Pan, Biomolecular condensates at the plasma membrane: Insights into plant cell signaling, Curr. Opin. Plant Biol. 84, 102697 (2025).
  14. J. E. Lee, P. I. Cathey, H. Wu, R. Parker, and G. K. Voeltz, Endoplasmic reticulum contact sites regulate the dynamics of membraneless organelles, Science 367, eaay7108 (2020).
  15. W. Snead, A. Jalihal, T. Gerbich, I. Seim, Z. Hu, and A. Gladfelter, Membrane surfaces regulate assembly of ribonucleoprotein condensates, Nat. Cell Biol. 24, 461 (2022).
  16. J. Agudo-Canalejo, S. W. Schultz, H. Chino, S. M. Migliano, C. Saito, I. Koyama-Honda, H. Stenmark, A. Brech, A. I. May, N. Mizushima, et al., Wetting regulates autophagy of phase-separated compartments and the cytosol, Nature (London) 591, 142 (2021).
  17. Y. Wang, S. Li, M. Mokbel, A. May, Z. Liang, Z. Yonglun, W. Wang, H. Zhang, F. Yu, K. Sporbeck, L. Jiang, S. Aland, J. Agudo-Canalejo, R. Knorr, and X. Fang, Biomolecular condensates mediate bending and scission of endosome membranes, Nature (London) 634, 1204 (2024).
  18. J. A. Morin, S. Wittmann, S. Choubey, A. Klosin, S. Golfier, A. A. Hyman, F. Jülicher, and S. W. Grill, Sequence-dependent surface condensation of a pioneer transcription factor on DNA, Nat. Phys. 18, 271 (2022).
  19. S. G. Gordon, A. A. Rodriguez, Y. Gu, K. D. Corbett, C. F. Lee, and O. Rog, The synaptonemal complex aligns meiotic chromosomes by wetting, Sci. Adv. 11, eadt5675 (2025).
  20. X. Zhao, G. Bartolucci, A. Honigmann, F. Jülicher, and C. A. Weber, Thermodynamics of wetting, prewetting and surface phase transitions with surface binding, New J. Phys. 23, 123003 (2021).
  21. M. Rouches, S. L. Veatch, and B. B. Machta, Surface densities prewet a near-critical membrane, Proc. Natl. Acad. Sci. USA 118, e2103401118 (2021).
  22. X. Zhao, S. Liese, A. Honigmann, F. Jülicher, and C. A. Weber, Theory of wetting dynamics with surface binding, New J. Phys. 26, 103025 (2024).
  23. M. N. Rouches and B. B. Machta, Protein-DNA co-condensation is prewetting to a collapsed polymer, Biophys. J. 124, 2280 (2025).
  24. J. W. Cahn, Critical point wetting, J. Chem. Phys. 66, 3667 (1977).
  25. P. G. de Gennes, Wetting: Statics and dynamics, Rev. Mod. Phys. 57, 827 (1985).
  26. D. Bonn and D. Ross, Wetting transitions, Rep. Prog. Phys. 64, 1085 (2001).
  27. P.-G. De Gennes, F. Brochard-Wyart, and D. Quéré, Capillarity and Wetting Phenomena: Drops, Bubbles, Pearls, Waves (Springer Science & Business Media, New York, 2003).
  28. P.-G. de Gennes, Scaling Concepts in Polymer Physics (Cornell University Press, Ithaca, NY, 1979).
  29. M. Rubinstein and R. H. Colby, Polymer Physics (Oxford University Press, New York, 2003).
  30. M. Doi, Soft Matter Physics (Oxford University Press, New York, 2013).
  31. C. P. Brangwynne, P. Tompa, and R. V. Pappu, Polymer physics of intracellular phase transitions, Nat. Phys. 11, 899 (2015).
  32. D. Kondepudi and I. Prigogine, Modern Thermodynamics: From Heat Engines to Dissipative Structures (John Wiley & Sons, Hoboken, 2014).
  33. J. W. Cahn and J. E. Hilliard, Free energy of a nonuniform system. I. Interfacial free energy, J. Chem. Phys. 28, 258 (1958).
  34. See Supplemental Material at http://link.aps.org/supplemental/10.1103/qyx1-nv48 for supplemental figures and movies.
  35. K. Binder, D. Landau, and M. Müller, Monte Carlo studies of wetting, interface localization and capillary condensation, J. Stat. Phys. 110, 1411 (2003).
  36. A. J. Liu, D. J. Durian, E. Herbolzheimer, and S. A. Safran, Wetting transitions in a cylindrical pore, Phys. Rev. Lett. 65, 1897 (1990).
  37. H. Tanaka, Dynamic interplay between phase separation and wetting in a binary mixture confined in a one-dimensional capillary, Phys. Rev. Lett. 70, 53 (1993).
  38. M. Y. Lin, S. K. Sinha, J. M. Drake, X.-l. Wu, P. Thiyagarajan, and H. B. Stanley, Study of phase separation of a binary fluid mixture in confined geometry, Phys. Rev. Lett. 72, 2207 (1994).
  39. L. MacDowell, M. Müller, and K. Binder, How do droplets on a surface depend on the system size? Colloids Surf. A 206, 277 (2002).
  40. D. Wu and J. Lin, Dataset, GitHub, 2026, https://github.com/wudaoning/wetting2026.

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Phys. Rev. Research 8, 033007– Published 6 July, 2026
  • Received 9 December 2025
  • Accepted 3 June 2026
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Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

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