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Imaging coexisting fluid domains in biomembrane models coupling curvature and line tension


Lipid bilayer membranes—ubiquitous in biological systems and closely associated with cell function—exhibit rich shape-transition behaviour, including bud formation1 and vesicle fission2. Membranes formed from multiple lipid components can laterally separate into coexisting liquid phases, or domains, with distinct compositions. This process, which may resemble raft formation in cell membranes, has been directly observed in giant unilamellar vesicles3,4. Detailed theoretical frameworks5,6,7,8,9,10,11 link the elasticity of domains and their boundary properties to the shape adopted by membranes and the formation of particular domain patterns, but it has been difficult to experimentally probe and validate these theories. Here we show that high-resolution fluorescence imaging using two dyes preferentially labelling different fluid phases directly provides a correlation between domain composition and local membrane curvature. Using freely suspended membranes of giant unilamellar vesicles, we are able to optically resolve curvature and line tension interactions of circular, stripe and ring domains. We observe long-range domain ordering in the form of locally parallel stripes and hexagonal arrays of circular domains, curvature-dependent domain sorting, and membrane fission into separate vesicles at domain boundaries. By analysing our observations using available membrane theory, we are able to provide experimental estimates of boundary tension between fluid bilayer domains.

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Figure 1: Two-photon microscopy images showing equatorial sections of GUVs with Lo + Ld phase coexistence.
Figure 2: Two-photon microscopy images of GUVs with Lo + Ld phase coexistence.


  1. Käs, J. & Sackmann, E. Shape transitions and shape stability of giant phospholipid vesicles in pure water induced by area-to-volume changes. Biophys. J. 60, 825–844 (1991)

    Article  Google Scholar 

  2. Döbereiner, H. G., Käs, J., Noppl, D., Sprenger, I. & Sackmann, E. Budding and fission of vesicles. Biophys. J. 65, 1396–1403 (1993)

    Article  Google Scholar 

  3. Dietrich, C. et al. Lipid rafts reconstituted in model membranes. Biophys. J. 80, 1417–1428 (2001)

    ADS  CAS  Article  Google Scholar 

  4. Veatch, S. L. & Keller, S. L. Organization in lipid membranes containing cholesterol. Phys. Rev. Lett. 89, 268101 (2002)

    ADS  Article  Google Scholar 

  5. Lipowsky, R. Budding of membranes induced by intramembrane domains. J. Phys. II France 2, 1825–1840 (1992)

    CAS  Article  Google Scholar 

  6. Leibler, S. & Andelman, D. Ordered and curved meso-structures in membranes and amphiphilic films. J. Phys. 48, 2013–2018 (1987)

    CAS  Article  Google Scholar 

  7. Seul, M. & Andelman, D. Domain shapes and patterns: The phenomenology of modulated phases. Science 267, 476–483 (1995)

    ADS  CAS  Article  Google Scholar 

  8. Jülicher, F. & Lipowsky, R. Shape transformations of vesicles with intramembrane domains. Phys. Rev. E 53, 2670–2683 (1996)

    ADS  Article  Google Scholar 

  9. Andelman, D., Kawakatsu, T. & Kawasaki, K. Equilibrium shape of two-component unilamellar membranes and vesicles. Europhys. Lett. 19, 57–62 (1992)

    ADS  CAS  Article  Google Scholar 

  10. Jiang, Y., Lookman, T. & Saxena, A. Phase separation and shape deformation of two-phase membranes. Phys. Rev. E 61, R57–R60 (2000)

    ADS  CAS  Article  Google Scholar 

  11. Kumar, P. B. S., Gompper, G. & Lipowsky, R. Budding dynamics of multicomponent membranes. Phys. Rev. Lett. 86, 3911–3914 (2001)

    ADS  Article  Google Scholar 

  12. Helfrich, W. Elastic properties of lipid bilayers: Theory and possible experiments. Z. Naturforsch. 28c, 693–703 (1973)

    Article  Google Scholar 

  13. Jenkins, J. T. Static equilibrium configurations of a model red blood cell. J. Math. Biol. 4, 149–169 (1976)

    Article  Google Scholar 

  14. Seifert, U. Curvature-induced lateral phase separation in two-component vesicles. Phys. Rev. Lett. 70, 1335–1338 (1993)

    ADS  CAS  Article  Google Scholar 

  15. Duwe, H. P. & Sackmann, E. Bending elasticity and thermal excitations of lipid bilayer vesicles: Modulation by solutes. Physica A 163, 410–428 (1990)

    ADS  CAS  Article  Google Scholar 

  16. Benvegnu, D. J. & McConnell, H. M. Line tension between liquid domains in lipid monolayers. J. Phys. Chem. 96, 6820–6824 (1992)

    CAS  Article  Google Scholar 

  17. Schneider, M. B., Jenkins, J. T. & Webb, W. W. Thermal fluctuations of large quasi-spherical bimolecular phospholipid vesicles. J. Phys. 45, 1457–1472 (1984)

    CAS  Article  Google Scholar 

  18. Helfrich, W. & Servuss, R. M. Undulations, steric interactions and cohesion of fluid membranes. Nuovo Cimento D 3, 137–151 (1984)

    ADS  Article  Google Scholar 

  19. Chen, C.-M., Higgs, P. G. & MacKintosh, F. C. Theory of fission for two-component lipid vesicles. Phys. Rev. Lett. 79, 1579–1582 (1997)

    ADS  CAS  Article  Google Scholar 

  20. Lipowsky, R. & Dimova, R. Domains in membranes and vesicles. J. Phys. Condens. Matter 15, S31–S45 (2003)

    ADS  CAS  Article  Google Scholar 

  21. Samsonov, A. V., Mihalyov, I. & Cohen, F. S. Characterization of cholesterol-sphingomyelin domains and their dynamics in bilayer membranes. Biophys. J. 81, 1486–1500 (2001)

    CAS  Article  Google Scholar 

  22. Debregeas, G., de Gennes, P.-G. & Brochard-Wyart, F. The life and death of “bare” viscous bubbles. Science 279, 1704–1707 (1998)

    ADS  CAS  Article  Google Scholar 

  23. Andelman, D., Brochard, F. & Joanny, J. F. Phase transitions in Langmuir monolayers of polar molecules. J. Chem. Phys. 86, 3673–3681 (1987)

    ADS  CAS  Article  Google Scholar 

  24. Bar-Ziv, R. & Moses, E. Instability and “pearling” states produced in tubular membranes by competition of curvature and tension. Phys. Rev. Lett. 73, 1392–1395 (1994)

    ADS  CAS  Article  Google Scholar 

  25. Wintz, W., Döbereiner, H. G. & Seifert, U. Starfish vesicles. Europhys. Lett. 33, 403–408 (1996)

    ADS  CAS  Article  Google Scholar 

  26. Mukherjee, S. & Maxfield, F. R. Role of membrane organization and membrane domains in endocytic lipid trafficking. Traffic 1, 203–211 (2000)

    CAS  Article  Google Scholar 

  27. Huttner, W. B. & Zimmerberg, J. Implications of lipid microdomains for membrane curvature, budding and fission. Curr. Opin. Cell Biol. 13, 478–484 (2001)

    CAS  Article  Google Scholar 

  28. Mathivet, L., Cribier, S. & Devaux, P. F. Shape change and physical properties of giant phospholipid vesicles prepared in the presence of an AC electric field. Biophys. J. 70, 1112–1121 (1996)

    ADS  CAS  Article  Google Scholar 

  29. Denk, W., Strickler, J. H. & Webb, W. W. Two-photon laser scanning fluorescence microscopy. Science 248, 73–76 (1990)

    ADS  CAS  Article  Google Scholar 

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We thank G. W. Feigenson, J. T. Jenkins, G. Gompper, J. Zimmerberg, A. K. Smith and A. T. Hammond for discussions. This work was supported in part by a CMBSTD grant of the W.M. Keck Foundation and an NIBIB-NIH grant to the Developmental Resource for Biophysical Imaging Opto-Electronics.

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Correspondence to Watt W. Webb.

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Supplementary information

Supplementary Figure 1: showing vesicle tracing and fitting results (PDF 1367 kb)


Supplementary Figure 1': Separate channels referring to the colour merged images of Figure 1 of the main text (PDF 1315 kb)

Supplementary Figure 2: Containing phase diagram information (PDF 670 kb)


Supplementary Figure 2': Separate channels referring to the colour merged images of Figure 2 of the main text (PDF 1351 kb)

Supplementary Movie: Showing line tension induced budding and fission (MOV 4510 kb)

Supplementary Methods, Figure and Movie legends (DOC 93 kb)

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Baumgart, T., Hess, S. & Webb, W. Imaging coexisting fluid domains in biomembrane models coupling curvature and line tension. Nature 425, 821–824 (2003).

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