Comparison of the liquid-ordered bilayer phases containing cholesterol or 7-dehydrocholesterol in modeling Smith-Lemli-Opitz syndrome.
The phase behavior of egg sphingomyelin (ESM) mixtures with cholesterol or 7-dehydrocholesterol (7-DHC) has been investigated by independent methods: fluorescence microscopy, X-ray diffraction, and electron spin resonance spectroscopy. In giant vesicles, cholesterol-enriched domains appeared as large and clearly delineated domains assigned to a liquid-ordered (Lo) phase. The domains containing 7-DHC were smaller and had more diffuse boundaries. Separation of a gel phase assigned by X-ray examination to pure sphingomyelin domains coexisting with sterol-enriched domains was observed at temperatures less than 38 degrees C in binary mixtures containing 10-mol% sterol. At higher sterol concentrations, the coexistence of liquid-ordered and liquid-disordered phases was evidenced in the temperature range 20 degrees -50 degrees C. Calculated electron density profiles indicated the location of 7-DHC was more loosely defined than cholesterol, which is localized precisely at a particular depth along the bilayer normal. ESR spectra of spin-labeled fatty acid partitioned in the liquid-ordered component showed a similar, high degree of order for both sterols in the center of the bilayer, but it was higher in the coexisting disordered phase for 7-DHC. The differences detected in the models of the lipid membrane matrix are said to initiate the deleterious consequences of the Smith-Lemli-Opitz syndrome.
Staneva
Galya
G
Institute of Biophysics, Bulgarian Academy of Sciences, Sofia, Bulgaria. gstaneva@obzor.bio21.bas.bg
Chachaty
Claude
C
Wolf
Claude
C
Quinn
Peter J
PJ
D002784:Cholesterol / Q000737:chemistry*; D003684:Dehydrocholesterols / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry*; D019082:Smith-Lemli-Opitz Syndrome; D013109:Sphingomyelins / Q000737:chemistry; D013113:Spin Labels; D014961:X-Ray Diffraction
D003684:Dehydrocholesterols; D008051:Lipid Bilayers; D008563:Membrane Lipids; D013109:Sphingomyelins; D013113:Spin Labels; D002784:Cholesterol; C016705:7-dehydrocholesterol