Mishra, Y. G. & Manavathi, B. Focal adhesion dynamics in cellular function and disease. Cell. Signal. 85, 110046 (2021).
Kaizuka, T. & Takumi, T. Postsynaptic density proteins and their involvement in neurodevelopmental disorders. J. Biochem. 163, 447–455 (2018).
Zihni, C., Mills, C., Matter, K. & Balda, M. S. Tight junctions: from simple barriers to multifunctional molecular gates. Nat. Rev. Mol. Cell Biol. 17, 564–580 (2016).
Courtney, A. H., Lo, W.-L. & Weiss, A. TCR signaling: mechanisms of initiation and propagation. Trends Biochem. Sci. 43, 108–123 (2018).
Su, X. et al. Phase separation of signaling molecules promotes T cell receptor signal transduction. Science 352, 595–599 (2016).
Zeng, M. et al. Reconstituted postsynaptic density as a molecular platform for understanding synapse formation and plasticity. Cell 174, 1172–1187 (2018).
Case, L. B., De Pasquale, M., Henry, L. & Rosen, M. K. Synergistic phase separation of two pathways promotes integrin clustering and nascent adhesion formation. eLife 11, e72588 (2022).
Snead, W. T. et al. Membrane surfaces regulate assembly of ribonucleoprotein condensates. Nat. Cell Biol. 24, 461–470 (2022).
Banjade, S. & Rosen, M. K. Phase transitions of multivalent proteins can promote clustering of membrane receptors. eLife 3, e04123 (2014).
Lin, C.-W. et al. A two-component protein condensate of the EGFR cytoplasmic tail and Grb2 regulates Ras activation by SOS at the membrane. Proc. Natl Acad. Sci. USA 119, e2122531119 (2022).
Wang, H.-Y. et al. Coupling of protein condensates to ordered lipid domains determines functional membrane organization. Sci. Adv. 9, eadf6205 (2023).
Case, L. B., Zhang, X., Ditlev, J. A. & Rosen, M. K. Stoichiometry controls activity of phase-separated clusters of actin signaling proteins. Science 363, 1093–1097 (2019).
McAffee, D. B. et al. Discrete LAT condensates encode antigen information from single pMHC:TCR binding events. Nat. Commun. 13, 7446 (2022).
Milovanovic, D., Wu, Y., Bian, X. & De Camilli, P. A liquid phase of synapsin and lipid vesicles. Science 361, 604–607 (2018).
Mangiarotti, A., Chen, N., Zhao, Z., Lipowsky, R. & Dimova, R. Wetting and complex remodeling of membranes by biomolecular condensates. Nat. Commun. 14, 2809 (2023).
Mangiarotti, A. et al. Biomolecular condensates modulate membrane lipid packing and hydration. Nat. Commun. 14, 6081 (2023).
Zeno, W. F., Johnson, K. E., Sasaki, D. Y., Risbud, S. H. & Longo, M. L. Dynamics of crowding-induced mixing in phase separated lipid bilayers. J. Phys. Chem. B 120, 11180–11190 (2016).
Yuan, F. et al. Membrane bending by protein phase separation. Proc. Natl Acad. Sci. USA 118, e2017435118 (2021).
Mondal, S. et al. Multivalent interactions between molecular components involved in fast endophilin mediated endocytosis drive protein phase separation. Nat. Commun. 13, 5017 (2022).
Lee, Y. et al. Transmembrane coupling of liquid-like protein condensates. Nat. Commun. 14, 8015 (2023).
Chung, J. K. et al. Coupled membrane lipid miscibility and phosphotyrosine-driven protein condensation phase transitions. Biophys. J. 120, 1257–1265 (2021).
Rouches, M., Veatch, S. L. & Machta, B. B. Surface densities prewet a near-critical membrane. Proc. Natl Acad. Sci. USA 118, e2103401118 (2021).
Nakanishi, H. & Fisher, M. E. Multicriticality of wetting, prewetting, and surface transitions. Phys. Rev. Lett. 49, 1565–1568 (1982).
Cahn, J. W. Critical point wetting. J. Chem. Phys. 66, 3667–3672 (1977).
Schmidt, J. W. & Moldover, M. R. A search for the prewetting line. J. Chem. Phys. 84, 4563–4568 (1986).
Zhao, X., Bartolucci, G., Honigmann, A., Jülicher, F. & Weber, C. A. Thermodynamics of wetting, prewetting and surface phase transitions with surface binding. New J. Phys. 23, 123003 (2021).
Veatch, S. L., Rogers, N., Decker, A. & Shelby, S. A. The plasma membrane as an adaptable fluid mosaic. Biochim. Biophys. Acta 1865, 184114 (2023).
Sezgin, E., Levental, I., Mayor, S. & Eggeling, C. The mystery of membrane organization: composition, regulation and roles of lipid rafts. Nat. Rev. Mol. Cell Biol. 18, 361–374 (2017).
Priftis, D. & Tirrell, M. Phase behaviour and complex coacervation of aqueous polypeptide solutions. Soft Matter 8, 9396–9405 (2012).
Baskin, J. M. et al. Copper-free click chemistry for dynamic in vivo imaging. Proc. Natl Acad. Sci. USA 104, 16793–16797 (2007).
Weakly, H. M. J. & Keller, S. L. Coupling liquid phases in 3D condensates and 2D membranes: successes, challenges, and tools. Biophys. J. 123, 1329–1341 (2024).
Ronceray, P., Zhang, Y., Liu, X. & Wingreen, N. S. Stoichiometry controls the dynamics of liquid condensates of associative proteins. Phys. Rev. Lett. 128, 038102 (2022).
Veatch, S. L. & Keller, S. L. Separation of liquid phases in giant vesicles of ternary mixtures of phospholipids and cholesterol. Biophys. J. 85, 3074–3083 (2003).
Symons, J. L. et al. Lipidomic atlas of mammalian cell membranes reveals hierarchical variation induced by culture conditions, subcellular membranes, and cell lineages. Soft Matter 17, 288–297 (2021).
Lee, S. et al. Reversible protein inactivation by optogenetic trapping in cells. Nat. Methods 11, 633–636 (2014).
Che, D. L., Duan, L., Zhang, K. & Cui, B. The dual characteristics of light-induced cryptochrome 2, homo-oligomerization and heterodimerization, for optogenetic manipulation in mammalian cells. ACS Synth. Biol. 4, 1124–1135 (2015).
Shelby, S. A., Castello-Serrano, I., Wisser, K. C., Levental, I. & Veatch, S. L. Membrane phase separation drives responsive assembly of receptor signaling domains. Nat. Chem. Biol. 19, 750–758 (2023).
Machta, B. B. et al. Conditions that stabilize membrane domains also antagonize n-alcohol anesthesia. Biophys. J. 111, 537–545 (2016).
Machta, B. B., Papanikolaou, S., Sethna, J. P. & Veatch, S. L. Minimal model of plasma membrane heterogeneity requires coupling cortical actin to criticality. Biophys. J. 100, 1668–1677 (2011).
Surviladze, Z., Dráberová, L., Kovářová, M., Boubelík, M. & Dráber, P. Differential sensitivity to acute cholesterol lowering of activation mediated via the high-affinity IgE receptor and Thy-1 glycoprotein. Eur. J. Immunol. 31, 1–10 (2001).
Wåhlén, E., Olsson, F., Söderberg, O., Lennartsson, J. & Heldin, J. Differential impact of lipid raft depletion on platelet-derived growth factor (PDGF)-induced ERK1/2 MAP-kinase, SRC and AKT signaling. Cell. Signal. 96, 110356 (2022).
Ottico, E. et al. Dynamics of membrane lipid domains in neuronal cells differentiated in culture1. J. Lipid Res. 44, 2142–2151 (2003).
Doktorova, M. et al. Cell membranes sustain phospholipid imbalance via cholesterol asymmetry. Cell 188, 2586–2602 (2025).
Suzuki, J., Umeda, M., Sims, P. J. & Nagata, S. Calcium-dependent phospholipid scrambling by TMEM16F. Nature 468, 834–838 (2010).
Clapham, D. E. Calcium signaling. Cell 131, 1047–1058 (2007).
Stefan, C. J. Endoplasmic reticulum–plasma membrane contacts: principals of phosphoinositide and calcium signaling. Curr. Opin. Cell Biol. 63, 125–134 (2020).
Volmer, R., van der Ploeg, K. & Ron, D. Membrane lipid saturation activates endoplasmic reticulum unfolded protein response transducers through their transmembrane domains. Proc. Natl Acad. Sci. USA 110, 4628–4633 (2013).
Sandhu, J. et al. Aster proteins facilitate nonvesicular plasma membrane to ER cholesterol transport in mammalian cells. Cell 175, 514–529 (2018).
Wiegand, T. et al. Actin polymerization counteracts prewetting of N-WASP on supported lipid bilayers. Proc. Natl Acad. Sci. USA 121, e2407497121 (2024).
Zhu, S. et al. Demixing is a default process for biological condensates formed via phase separation. Science 384, 920–928 (2024).
Lin, C.-C. et al. Receptor tyrosine kinases regulate signal transduction through a liquid–liquid phase separated state. Mol. Cell. 82, 1089–1106 (2022).
Pombo-García, K., Adame-Arana, O., Martin-Lemaitre, C., Jülicher, F. & Honigmann, A. Membrane prewetting by condensates promotes tight-junction belt formation. Nature 632, 647–655 (2024).
Simons, K. & Ikonen, E. Functional rafts in cell membranes. Nature 387, 569–572 (1997).
Case, L. B., Ditlev, J. A. & Rosen, M. K. Regulation of transmembrane signaling by phase separation. Annu. Rev. Biophys. 48, 465–494 (2019).
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).
Alberti, S., Gladfelter, A. & Mittag, T. Considerations and challenges in studying liquid–liquid phase separation and biomolecular condensates. Cell 176, 419–434 (2019).
Banjade, S., Zhu, L., Jorgensen, J. R., Suzuki, S. W. & Emr, S. D. Recruitment and organization of ESCRT-0 and ubiquitinated cargo via condensation. Sci. Adv. 8, eabm5149 (2022).
Kim, S., Okafor, K. K., Tabuchi, R., Briones, C. & Lee, I.-H. Phase separation clustering of poly ubiquitin cargos on ternary mixture lipid membranes by synthetically cross-linked ubiquitin binder peptides. Biochemistry 64, 1212–1221 (2025).
Guo, P. et al. PI4P-mediated solid-like Merlin condensates orchestrate Hippo pathway regulation. Science 385, eadf4478 (2024).
Hsu, C.-P., Hordeichyk, A., Aretz, J., Fässler, R. & Bausch, A. R. Synergistic effect of PIP2 and PIP3 on membrane-induced phase separation of integrin complexes. Biophys. J. 0, S0006–3495(25)00238–3 (2025).
Wong, L. E. et al. Tripartite phase separation of two signal effectors with vesicles priming B cell responsiveness. Nat. Commun. 11, 848 (2020).
Tillu, V. A. et al. Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation. Nat. Commun. 12, 931 (2021).
Shnyrova, A. V. et al. Vesicle formation by self-assembly of membrane-bound matrix proteins into a fluidlike budding domain. J. Cell Biol. 179, 627–633 (2007).
Carlson, L.-A., Bai, Y., Keane, S. C., Doudna, J. A. & Hurley, J. H. Reconstitution of selective HIV-1 RNA packaging in vitro by membrane-bound Gag assemblies. eLife 5, e14663 (2016).
Tan, R. et al. Microtubules gate tau condensation to spatially regulate microtubule functions. Nat. Cell Biol. 21, 1078–1085 (2019).
Rouches, M. N. & Machta, B. B. Protein–DNA co-condensation is prewetting to a collapsed polymer. Biophys. J. 124, 2280–2290 (2025).
Pyenta, P. S., Holowka, D. & Baird, B. Cross-correlation analysis of inner-leaflet-anchored green fluorescent protein co-redistributed with IgE receptors and outer leaflet lipid raft components. Biophys. J. 80, 2120–2132 (2001).
Ma, W. & Mayr, C. A membraneless organelle associated with the endoplasmic reticulum enables 3′UTR-mediated protein–protein interactions. Cell 175, 1492–1506 (2018).
Bisaria, A., Hayer, A., Garbett, D., Cohen, D. & Meyer, T. Membrane-proximal F-actin restricts local membrane protrusions and directs cell migration. Science 368, 1205–1210 (2020).
Römer, A., Rawat, D., Linn, T. & Petry, S. F. Preparation of fatty acid solutions exerts significant impact on experimental outcomes in cell culture models of lipotoxicity. Biol. Methods Protoc. 7, bpab023 (2022).
Gerstle, Z., Desai, R. & Veatch, S. L. in Chemical and Biochemical Approaches for the Study of Anesthetic Function Part B 129–150 (Elsevier, 2018).
