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Differential Modulation of Membrane Structure and Fluctuations by Plant Sterols and Cholesterol

Institute of Biophysics and Nanosystems Research, Austrian Academy of Sciences, A-8042 Graz, Austria

Correspondence: Address reprint requests to Georg Pabst, Institute of Biophysics and Nanosystems Research, Austrian Academy of Sciences, Schmiedlstr. 6, A-8042 Graz, Austria. Tel.: 43-316-4120-342; Fax: 43-316-4120-390; E-mail: Georg.Pabst{at}oeaw.ac.at.

We have studied the concentration and temperature dependent influence of cholesterol, stigmasterol, and sitosterol on the global structure and the bending fluctuations of fluid dimyristoyl phosphatidylcholine and palmitoyl oleoyl phosphatidylcholine bilayers applying small-angle x-ray scattering, as well as dilatometry and ultrasound velocimetry. Independent of the lipid matrix, cholesterol was found to be most efficient in modulating bilayer thickness and elasticity, followed by sitosterol and stigmasterol. This can be attributed to the additional ethyl groups and double bond at the C₁₇ alkyl side-chain of the two plant sterols. Hence, it seems that some flexibility of the sterol hydrocarbon chain is needed to accommodate within the lipid bilayer. In addition, we did not observe two populations of membranes within the putative liquid-ordered/liquid-disordered phase coexistence regime of binary sterol/lipid mixtures. Instead, the diffraction patterns could be interpreted in terms of a uniform phase. This lends further support to the idea of compositional fluctuations of unstable sterol rich domains recently brought up by fluorescence microscopy experiments, which contrasts the formation of stable domains within the miscibility gap of binary lipid/sterol mixtures.