JOURNAL OF SHANDONG UNIVERSITY(NATURAL SCIENCE) ›› 2025, Vol. 60 ›› Issue (10): 1-12.doi: 10.6040/j.issn.1671-9352.0.2025.251

   

Interfacial tension of biomolecular condensates

LI Guangle1, YAN Xuehai1,2,3*   

  1. 1. State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China;
    2. School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China;
    3. Center for Mesoscience, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China
  • Published:2025-10-17

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Abstract: Biomolecular condensates, as membraneless organelles formed through liquid-liquid phase separation, play critical roles in cellular spatiotemporal organization and functional regulation. This review focuses on their interfacial tension, a core physicochemical parameter, and systematically elucidates its thermodynamic foundations, measurement methods, and regulatory mechanisms on condensate stability. Based on the Flory-Huggins model, it reveals the driving role of interfacial tension in condensate formation, coarsening, multiphase assembly, and interactions with cellular structures. Various in vitro and in situ measurement techniques, including optical tweezers-induced fusion, micropipette aspiration, and condensate shape analysis, are reviewed, along with comparisons of interfacial properties between biomolecular condensates and traditional oil-water systems. Additionally, recent advances in modulating interfacial tension to enhance condensate stability using intrinsically disordered protein as Pickering stabilizers and amphiphilic block copolymers are discussed. These studies not only deepen the understanding of the physicochemical mechanisms underlying cellular compartmentalization but also provide potential new strategies for treating diseases associated with aberrant phase separation, such as neurodegenerative disorders and cancers.

Key words: biomolecular condensate, interfacial tension, liquid-liquid phase separation

CLC Number: 

  • O648
[1] BANANI S F, LEE H O, HYMAN A A, et al. Biomolecular condensates: organizers of cellular biochemistry[J]. Nature Reviews Molecular Cell Biology, 2017, 18(5):285-298.
[2] LYON A S, PEEPLES W B, ROSEN M K. A framework for understanding the functions of biomolecular condensates across scales[J]. Nature Reviews Molecular Cell Biology, 2020, 22(3):215-235.
[3] VISSER B S, LIPINSKI W P, SPRUIJT E. The role of biomolecular condensates in protein aggregation[J]. Nature Reviews Chemistry, 2024, 8(9):686-700.
[4] VILLEGAS J A, HEIDENREICH M, LEVY E D. Molecular and environmental determinants of biomolecular condensate formation[J]. Nature Chemical Biology, 2022, 18(12):1319-1329.
[5] GAO Y F, LI X, LI P L, et al. A brief guideline for studies of phase-separated biomolecular condensates[J]. Nature Chemical Biology, 2022, 18(12):1307-1318.
[6] HYMAN A A, WEBER C A, JÜLICHER F. Liquid-liquid phase separation in biology[J]. Annual Review of Cell and Developmental Biology, 2014, 30:39-58.
[7] ALBERTI S, GLADFELTER A, MITTAG T. Considerations and challenges in studying liquid-liquid phase separation and biomolecular condensates[J]. Cell, 2019, 176(3):419-434.
[8] SHIN Y, BRANGWYNNE C P. Liquid phase condensation in cell physiology and disease[J]. Science, 2017, 357(6357):eaaf4382.
[9] ABYZOV A, BLACKLEDGE M, ZWECKSTETTER M. Conformational dynamics of intrinsically disordered proteins regulate biomolecular condensate chemistry[J]. Chemical Reviews, 2022, 122(6):6719-6748.
[10] ALBERTI S, HYMAN A A. Biomolecular condensates at the nexus of cellular stress, protein aggregation disease and ageing[J]. Nature Reviews Molecular Cell Biology, 2021, 22(3):196-213.
[11] GOUVEIA B, KIM Y, SHAEVITZ J W, et al. Capillary forces generated by biomolecular condensates[J]. Nature, 2022, 609(7926):255-264.
[12] ZHOU H X, KOTA D, QIN S B, et al. Fundamental aspects of phase-separated biomolecular condensates[J]. Chemical Reviews, 2024, 124(13):8550-8595.
[13] SHI S W, RUSSELL T P. Nanoparticle assembly at liquid-liquid interfaces: from the nanoscale to mesoscale[J]. Advanced Materials, 2018, 30(44):1800714.
[14] CUI M M, EMRICK T,RUSSELL T P.Stabilizing liquid drops in nonequilibrium shapes by the interfacial jamming of nanoparticles[J]. Science, 2013, 342(6157):460-463.
[15] LIU X B, KENT N, CEBALLOS A, et al. Reconfigurable ferromagnetic liquid droplets[J]. Science, 2019, 365(6450):264-267.
[16] LI G L, ZUO Y Y. Molecular and colloidal self-assembly at the oil-water interface[J]. Current Opinion in Colloid & Interface Science, 2022, 62:101639.
[17] FERIC M, VAIDYA N, HARMON T S, et al. Coexisting liquid phases underlie nucleolar subcompartments[J]. Cell, 2016, 165(7):1686-1697.
[18] AGUDO-CANALEJO J, SCHULTZ S W, CHINO H, et al. Wetting regulates autophagy of phase-separated compartments and the cytosol[J]. Nature, 2021, 591(7848):142-146.
[19] HERNÁNDEZ-VEGA A, BRAUN M, SCHARREL L, et al. Local nucleation of microtubule bundles through tubulin concentration into a condensed tau phase[J]. Cell Reports, 2017, 20(10):2304-2312.
[20] SETRU S U, GOUVEIA B, ALFARO-ACO R, et al. A hydrodynamic instability drives protein droplet formation on microtubules to nucleate branches[J]. Nature Physics, 2021, 17(4):493-498.
[21] KUSUMAATMAJA H, MAY A I, FEENEY M, et al. Wetting of phase-separated droplets on plant vacuole membranes leads to a competition between tonoplast budding and nanotube formation[J]. Proceedings of the National Academy of Sciences of the United States of America, 2021, 118(36):e2024109118.
[22] WHEELER J R, MATHENY T, JAIN S, et al. Distinct stages in stress granule assembly and disassembly[J]. eLife, 2016, 5:e18413.
[23] KILIC S, LEZAJA A, GATTI M, et al. Phase separation of 53BP1 determines liquid-like behavior of DNA repair compartments[J]. The EMBO Journal, 2019, 38(16):e101379.
[24] CONICELLA A E, ZERZE G H, MITTAL J, et al. ALS mutations disrupt phase separation mediated by α-helical structure in the TDP-43 low-complexity C-terminal domain[J]. Structure, 2016, 24(9):1537-1549.
[25] BOIJA A, KLEIN I A, YOUNG R A. Biomolecular condensates and cancer[J]. Cancer Cell, 2021, 39(2):174-192.
[26] RUBINSTEIN M, COLBY R H. Polymer physics[M]. Cambridge:Oxford University Press, 2003.
[27] SHIMOBAYASHI S F, RONCERAY P, SANDERS D W, et al. Nucleation landscape of biomolecular condensates[J]. Nature, 2021, 599(7885):503-506.
[28] NARAYANAN A, MERIIN A, ANDREWS J O, et al. A first order phase transition mechanism underlies protein aggregation in mammalian cells[J]. eLife, 2019, 8:e39695.
[29] AARTS D G A L, SCHMIDT M, LEKKERKERKER H N W. Direct visual observation of thermal capillary waves[J]. Science, 2004, 304(5672):847-850.
[30] DILL K, BROMBERG S. Molecular driving forces: statistical thermodynamics in biology, chemistry, physics, and nanoscience[M]. 2nd ed. New York: Garland Science, 2010.
[31] ELBAUM-GARFINKLE S, KIM Y,SZCZEPANIAK K, et al. The disordered P granule protein LAF-1 drives phase separation into droplets with tunable viscosity and dynamics[J]. Proceedings of the National Academy of Sciences, 2015, 112(23):7189-7194.
[32] NAKASHIMA K K, VAN HAREN M H I, ANDRÉ A A M, et al. Active coacervate droplets are protocells that grow and resist Ostwald ripening[J]. Nature Communications, 2021, 12:3819.
[33] EGGERS J, LISTER J R, STONE H A. Coalescence of liquid drops[J]. Journal of Fluid Mechanics, 1999, 401:293-310.
[34] ROSOWSKI K A, SAI T Q, VIDAL-HENRIQUEZ E, et al. Elastic ripening and inhibition of liquid-liquid phase separation[J]. Nature Physics, 2020, 16(4):422-425.
[35] MANGIAROTTI A, CHEN N N, ZHAO Z L, et al. Wetting and complex remodeling of membranes by biomolecular condensates[J]. Nature Communications, 2023, 14:2809.
[36] ZARZAR L D, SRESHT V, SLETTEN E M, et al. Dynamically reconfigurable complex emulsions via tunable interfacial tensions[J]. Nature, 2015, 518(7540):520-524.
[37] FEI J Y, JADALIHA M, HARMON T S, et al. Quantitative analysis of multilayer organization of proteins and RNA in nuclear speckles at super resolution[J]. Journal of Cell Science, 2017, 130(24):4180-4192.
[38] KAUR T, RAJU M, ALSHAREEDAH I, et al. Sequence-encoded and composition-dependent protein-RNA interactions control multiphasic condensate morphologies[J]. Nature Communications, 2021, 12:872.
[39] WANG Z, LOU J Z, ZHANG H. Essence determines phenomenon: Assaying the material properties of biological condensates[J]. Journal of Biological Chemistry, 2022, 298(4):101782.
[40] WANG H, KELLEY F M, MILOVANOVIC D, et al. Surface tension and viscosity of protein condensates quantified by micropipette aspiration[J]. Biophysical Reports, 2021, 1(1):100011.
[41] ALSHAREEDAH I, MOOSA M M, PHAM M, et al. Programmable viscoelasticity in protein-RNA condensates with disordered sticker-spacer polypeptides[J]. Nature Communications, 2021, 12:6620.
[42] ALSHAREEDAH I, THURSTON G M, BANERJEE P R. Quantifying viscosity and surface tension of multicomponent protein-nucleic acid condensates[J]. Biophysical Journal, 2021, 120(7):1161-1169.
[43] FISHER R S, ELBAUM-GARFINKLE S. Tunable multiphase dynamics of arginine and lysine liquid condensates[J]. Nature Communications, 2020, 11:4628.
[44] ALSHAREEDAH I, BORCHERDS W M, COHEN S R, et al. Sequence-specific interactions determine viscoelasticity and ageing dynamics of protein condensates[J]. Nature Physics, 2024, 20(9):1482-1491.
[45] CATALÀ-CASTRO F, ORTIZ-VÁSQUEZ S, MARTÍNEZ-FERNÁNDEZ C, et al. Measuring age-dependent viscoelasticity of organelles, cells and organisms with time-shared optical tweezer microrheology[J]. Nature Nanotechnology, 2025, 20(3):411-420.
[46] TASSIERI M, EVANS R M L, WARREN R L, et al. Microrheology with optical tweezers: data analysis[J]. New Journal of Physics, 2012, 14(11):115032.
[47] CAO S P, ZHOU P, SHEN G Z, et al. Binary peptide coacervates as an active model for biomolecular condensates[J]. Nature Communications, 2025, 16:2407.
[48] CAO S, FAN W, YUAN C Q, et al. Peptide nanoarchitectonics beyond long-range ordering[J]. Advances in Colloid and Interface Science, 2025, 343:103556.
[49] LI G L, YUAN C Q, YAN X H. Peptide-mediated liquid-liquid phase separation and biomolecular condensates[J]. Soft Matter, 2025, 21(10):1781-1812.
[50] YUAN C Q, XING R R, CUI J, et al. Multistep desolvation as a fundamental principle governing peptide self-assembly through liquid-liquid phase separation[J]. CCS Chemistry, 2024, 6(1):255-265.
[51] ZHOU P, XING R R, LI Q, et al. Steering phase-separated droplets to control fibrillar network evolution of supramolecular peptide hydrogels[J]. Matter, 2023, 6(6):1945-1963.
[52] YUAN C Q, LEVIN A, CHEN W, et al. Nucleation and growth of amino acid and peptide supramolecular polymers through liquid-liquid phase separation[J]. AngewandteChemie International Edition, 2019, 58(50):18116-18123.
[53] WANG H, HOFFMANN C, TROMM J V, et al. Live-cell quantification reveals viscoelastic regulation of synapsin condensates by α-synuclein[J]. Science Advances, 2025, 11(16):eads7627.
[54] DRURY J L, DEMBO M. Hydrodynamics of micropipette aspiration[J]. Biophysical Journal, 1999, 76(1):110-128.
[55] ISRAELACHVILI J N. Intermolecular and surface forces[M]. 3rd ed. Amsterdam: Elsevier, 2011
[56] GUEVORKIAN K, COLBERT M J, DURTH M, et al. Aspiration of biological viscoelastic drops[J]. Physical Review Letters, 2010, 104(21):218101.
[57] HANSEN F K. Surface tension by image analysis: fast and automatic measurements of pendant and sessile drops and bubbles[J]. Journal of Colloid and Interface Science, 1993, 160(1):209-217.
[58] THAN P, PREZIOSI L, JOSEPHL D D, et al. Measurement of interfacial tension between immiscible liquids with the spinning road tensiometer[J]. Journal of Colloid and Interface Science, 1988, 124(2):552-559.
[59] NEESON M J, TABOR R F, GRIESER F, et al. Compound sessile drops[J]. Soft Matter, 2012, 8(43):11042.
[60] LI G L, DEL HIERRO G R, DI J Z, et al. Compound drop shape analysis with the Neumann number[J]. Langmuir, 2020, 36(26):7619-7626.
[61] SATHYAVAGEESWARAN A, BONESSO SABADINI J, PERRY S L. Self-assembling polypeptides in complex coacervation[J]. Accounts of Chemical Research, 2024, 57(3):386-398.
[62] AUMILLER W M, KEATING C D. Phosphorylation-mediated RNA/peptide complex coacervation as a model for intracellular liquid organelles[J]. Nature Chemistry, 2015, 8(2):129-137.
[63] LU T M, NAKASHIMA K K, SPRUIJT E. Temperature-responsive peptide-nucleotide coacervates[J]. The Journal of Physical Chemistry B, 2021, 125(12):3080-3091.
[64] FOLKMANN A W, PUTNAM A, LEE C F, et al. Regulation of biomolecular condensates by interfacial protein clusters[J]. Science, 2021, 373(6560):1218-1224.
[65] TANG D, ZHU J, WANG H, et al. Universal membranization of synthetic coacervates and biomolecular condensates towards ultrastability and spontaneous emulsification[J]. Nature Chemistry, 2025, 17(6):911-923.
[66] YIM W, JIN Z C, CHANG Y C, et al. Polyphenol-stabilized coacervates for enzyme-triggered drug delivery[J]. Nature Communications, 2024, 15:7295.
[67] AGRAWAL A, DOUGLAS J F, TIRRELL M, et al. Manipulation of coacervate droplets with an electric field[J]. Proceedings of the National Academy of Sciences of the United States of America, 2022, 119(32):e2203483119.
[68] PIR CAKMAK F, MARIANELLI A M, KEATING C D. Phospholipid membrane formation templated by coacervate droplets[J]. Langmuir, 2021, 37(34):10366-10375.
[69] JI Y, LIN Y Y, QIAO Y. Plant cell-inspired membranization of coacervate protocells with a structured polysaccharide layer[J]. Journal of the American Chemical Society, 2023, 145(23):12576-12585.
[70] MASON A F, BUDDINGH B C, WILLIAMS D S, et al. Hierarchical self-assembly of a copolymer-stabilized coacervate protocell[J]. Journal of the American Chemical Society, 2017, 139(48):17309-17312.
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