Effect of Cyclodextrin Structure upon Interaction of Cyclodextrin with Different Lipids Incorporated into Model Membrane Vesicles

Abstract

We have used methyl-beta- cyclodextrin (MbCD) to exchange membrane lipids between different vesicles in order to prepare model membrane vesicles with lipid asymmetry. To determine how to improve the efficiency of this method, the binding of lipids to various cyclodextrins (CDs) was investigated. The decrease in light scattering of multilamellar vesicles and the change in Förster resonance energy transfer (FRET) of labeled lipids incorporated into small unilamellar vesicles comprised primarily of unlabeled lipids were used to detect when vesicles are dissolved by binding of lipids to CD. A different FRET assay was used to detect when CDs catalyzed lipid exchange under conditions that vesicles do not dissolve. The effects of CD ring size (6, 7 or 8 sugar rings), substituants (hydroxy propyl, methyl, carboxymethyl and sulfate) and CD concentration were examined. It was found that while MbCD has the ability to dissolve lipid vesicles, most other CDs do not, although they are able to exchange lipids between vesicles. At lower MbCD concentrations, even MbCD loses the ability to dissolve vesicles, it retains the ability to exchange lipids. For MbCD, the concentration needed to dissolve about half of the vesicles was not strongly affected by lipid headgroup or acyl chain saturation, although there seemed to be some effect of acyl chain length.