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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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)
Döbereiner, H. G., Käs, J., Noppl, D., Sprenger, I. & Sackmann, E. Budding and fission of vesicles. Biophys. J. 65, 1396–1403 (1993)
Dietrich, C. et al. Lipid rafts reconstituted in model membranes. Biophys. J. 80, 1417–1428 (2001)
Veatch, S. L. & Keller, S. L. Organization in lipid membranes containing cholesterol. Phys. Rev. Lett. 89, 268101 (2002)
Lipowsky, R. Budding of membranes induced by intramembrane domains. J. Phys. II France 2, 1825–1840 (1992)
Leibler, S. & Andelman, D. Ordered and curved meso-structures in membranes and amphiphilic films. J. Phys. 48, 2013–2018 (1987)
Seul, M. & Andelman, D. Domain shapes and patterns: The phenomenology of modulated phases. Science 267, 476–483 (1995)
Jülicher, F. & Lipowsky, R. Shape transformations of vesicles with intramembrane domains. Phys. Rev. E 53, 2670–2683 (1996)
Andelman, D., Kawakatsu, T. & Kawasaki, K. Equilibrium shape of two-component unilamellar membranes and vesicles. Europhys. Lett. 19, 57–62 (1992)
Jiang, Y., Lookman, T. & Saxena, A. Phase separation and shape deformation of two-phase membranes. Phys. Rev. E 61, R57–R60 (2000)
Kumar, P. B. S., Gompper, G. & Lipowsky, R. Budding dynamics of multicomponent membranes. Phys. Rev. Lett. 86, 3911–3914 (2001)
Helfrich, W. Elastic properties of lipid bilayers: Theory and possible experiments. Z. Naturforsch. 28c, 693–703 (1973)
Jenkins, J. T. Static equilibrium configurations of a model red blood cell. J. Math. Biol. 4, 149–169 (1976)
Seifert, U. Curvature-induced lateral phase separation in two-component vesicles. Phys. Rev. Lett. 70, 1335–1338 (1993)
Duwe, H. P. & Sackmann, E. Bending elasticity and thermal excitations of lipid bilayer vesicles: Modulation by solutes. Physica A 163, 410–428 (1990)
Benvegnu, D. J. & McConnell, H. M. Line tension between liquid domains in lipid monolayers. J. Phys. Chem. 96, 6820–6824 (1992)
Schneider, M. B., Jenkins, J. T. & Webb, W. W. Thermal fluctuations of large quasi-spherical bimolecular phospholipid vesicles. J. Phys. 45, 1457–1472 (1984)
Helfrich, W. & Servuss, R. M. Undulations, steric interactions and cohesion of fluid membranes. Nuovo Cimento D 3, 137–151 (1984)
Chen, C.-M., Higgs, P. G. & MacKintosh, F. C. Theory of fission for two-component lipid vesicles. Phys. Rev. Lett. 79, 1579–1582 (1997)
Lipowsky, R. & Dimova, R. Domains in membranes and vesicles. J. Phys. Condens. Matter 15, S31–S45 (2003)
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)
Debregeas, G., de Gennes, P.-G. & Brochard-Wyart, F. The life and death of “bare” viscous bubbles. Science 279, 1704–1707 (1998)
Andelman, D., Brochard, F. & Joanny, J. F. Phase transitions in Langmuir monolayers of polar molecules. J. Chem. Phys. 86, 3673–3681 (1987)
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)
Wintz, W., Döbereiner, H. G. & Seifert, U. Starfish vesicles. Europhys. Lett. 33, 403–408 (1996)
Mukherjee, S. & Maxfield, F. R. Role of membrane organization and membrane domains in endocytic lipid trafficking. Traffic 1, 203–211 (2000)
Huttner, W. B. & Zimmerberg, J. Implications of lipid microdomains for membrane curvature, budding and fission. Curr. Opin. Cell Biol. 13, 478–484 (2001)
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)
Denk, W., Strickler, J. H. & Webb, W. W. Two-photon laser scanning fluorescence microscopy. Science 248, 73–76 (1990)
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.
The authors declare that they have no competing financial interests.
Supplementary Figure 1': Separate channels referring to the colour merged images of Figure 1 of the main text (PDF 1315 kb)
Supplementary Figure 2': Separate channels referring to the colour merged images of Figure 2 of the main text (PDF 1351 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). https://doi.org/10.1038/nature02013
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