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

Abstract

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.

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Acknowledgements

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)

41586_2003_BFnature02013_MOESM2_ESM.pdf

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)

41586_2003_BFnature02013_MOESM4_ESM.pdf

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). https://doi.org/10.1038/nature02013

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