Sphingomyelin-cholesterol superlattices as detected with Langmuir isotherms: their potential role in myelin and demyelination - eScholarship

Author(s): Koopman, Erik; Husted, Cynthia A., Ph.D. | Abstract: ABSTRACT In Multiple Sclerosis (MS) and Experimental Allergic Encephalomyelitis (EAE) in the common marmoset, demyelination appears to result from loss of adhesion between adjacent myelin lamellae and the formation of small myelin vesicles. Although proteins are involved in maintaining normal myelin structure, lipids may play an essential role in myelin stability. In the current study we focused on the effect that disturbed ratios of sphingomyelin (SM) and cholesterol may have on the regular distribution of those molecules. Mixtures of egg SMs (saturated) and bovine brain SMs (partially unsaturated) with cholesterol were made and examined with Langmuir isotherms. The cholesterol-induced condensations of the average molecular areas were determined by classic mean molecular area vs. composition plots. The results showed that egg SMs are significantly more expanded than bovine brain SMs, contrary to the fact that they are more saturated. We believe this is due to the fact that two-dimensional phase transitions of the predominant acyl chain species of egg SM generally occur at lower pressures compared to the predominant species in bovine brain SM due to their shorter acyl chain lengths. Furthermore we found that just beyond 22.2 mol% cholesterol, a predicted superlattice concentration, the condensation effect of cholesterol dramatically increases. We explain this by the fact that just beyond this point, the membrane regions containing only SM molecules have completely disappeared.