Cholesterol's Interfacial Interactions with Galactosylceramides

Shaukat Ali, Janice M. Smaby, Howard L. Brockman, Rhoderick E Brown

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Recently, the influence of acyl structure on galactosylceramide's (GalCer) interfacial phase behavior was studied [Ali, S., Smaby, J. M., & Brown, R. E. (1993) Biochemistry 32, 11696–11703]. Here, we show that acyl structure is a key parameter controlling GalCer's ability to interact with cholesterol. Different chain-pure GalCer species containing saturated (24:0, 18:0, or 10:0), or unsaturated (24:1Δ15, 22:1Δ13, or 18:2Δ9,12) acyl chains were synthesized. After measurement of the force-area behavior of mixed cholesterol/GalCer films at 24 °C, the average molecular area and average compressibility were determined as a function of film composition. Cholesterol exerts only a slight condensing effect when the GalCer species are liquid-ordered [liquid-condensed], with maximum condensation occurring near 0.25 mole fraction. However, cholesterol exerts a marked condensing effect on liquid-disordered (liquid-expanded) GalCer species regardless of whether the acyl chain is saturated or unsaturated. Maximum condensation occurs at cholesterol mole fractions between 0.3 and 0.4. We also compared cholesterol's relative condensing effect on liquid-expanded GalCer versus sphingomyelin. Cholesterol's condensation of either bovine brain or egg sphingomyelin is 25–30% greater than that observed with different liquid-expanded GalCer species. Aside from average area behavior, we assessed cholesterol's interfacial interactions with the various sphingolipids by determining the average compressibility as a function of composition. The compressibility of condensed GalCer derivatives changes very little upon addition of cholesterol. In contrast, cholesterol causes dramatic changes when combined with liquid-expanded GalCer derivatives, which all have compressibilities 4–5-fold higher than bovine brain GalCer. The nature of the cholesterol-induced change in average compressibility for liquid-expanded GalCer derivatives depends on acyl structure and surface pressure.

Original languageEnglish (US)
Pages (from-to)2900-2906
Number of pages7
JournalBiochemistry
Volume33
Issue number10
DOIs
StatePublished - Mar 1 1994

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