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Formation of Cholesterol-Rich Supported Membranes Using Solvent-Assisted Lipid Self-Assembly
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    Formation of Cholesterol-Rich Supported Membranes Using Solvent-Assisted Lipid Self-Assembly
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    School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
    Centre for Biomimetic Sensor Science, Nanyang Technological University, 50 Nanyang Drive, Singapore 637553, Singapore
    § School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459, Singapore
    Department of Biomedical Engineering and of Chemical Engineering & Materials Science, University of California, Davis, California 95616, United States
    Austrian Institute of Technology (AIT), Donau-City-Strasse 1, 1220 Vienna, Austria
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    Langmuir

    Cite this: Langmuir 2014, 30, 44, 13345–13352
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    https://doi.org/10.1021/la5034433
    Published October 6, 2014
    Copyright © 2014 American Chemical Society

    Abstract

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    This paper describes the application of a solvent-exchange method to prepare supported membranes containing high fractions of cholesterol (up to ∼57 mol %) in an apparent equilibrium. The method exploits the phenomenon of reverse-phase evaporation, in which the deposition of lipids in alcohol (e.g., isopropanol) is followed by the slow removal of the organic solvent from the water-alcohol mixture. This in turn induces a series of lyotropic phase transitions successively producing inverse-micelles, monomers, micelles, and vesicles in equilibrium with supported bilayers at the contacting solid surface. By using the standard cholesterol depletion by methyl-β-cyclodextrin treatment, a quartz crystal microbalance with dissipation monitoring assay confirms that the cholesterol concentration in the supported membranes is comparable to that in the surrounding bulk phase. A quantitative characterization of the biophysical properties of the resultant bilayer, including lateral diffusion constants and phase separation, using epifluorescence microscopy and atomic force microscopy establishes the formation of laterally contiguous supported lipid bilayers, which break into a characteristic domain-pattern of coexisting phases in a cholesterol concentration-dependent manner. With increasing cholesterol fraction in the supported bilayer, the size of the domains increases, ultimately yielding two-dimensional cholesterol bilayer domains near the solubility limit. A unique feature of the approach is that it enables preparation of supported membranes containing limiting concentrations of cholesterol near the solubility limit under equilibrium conditions, which cannot be obtained using conventional techniques (i.e., vesicle fusion).

    Copyright © 2014 American Chemical Society

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    More detailed information is provided about QCM-D tracking of supported membranes formed via the SALB and vesicle fusion methods (Figures S1 and S3), epifluorescence microscopy images of supported membranes formed via the SALB and vesicle fusion methods (Figures S2 and S4), and QCM-D characterization of cholesterol content in supported lipid bilayers (Figures S5 and S6). This material is available free of charge via the Internet at http://pubs.acs.org.

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    This article is cited by 53 publications.

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    Langmuir

    Cite this: Langmuir 2014, 30, 44, 13345–13352
    Click to copy citationCitation copied!
    https://doi.org/10.1021/la5034433
    Published October 6, 2014
    Copyright © 2014 American Chemical Society

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