Lactosylceramide: Lateral Interactions with Cholesterol

¹ University of Minnesota

^* To whom correspondence should be addressed. E-mail: reb{at}umn.edu.

Submitted on March 10, 2006
Revised on April 11, 2006
Accepted on 14 June 2006

	Abstract

Lactosylceramide (LacCer) is a key intermediate in glycosphingolipid metabolism and is highly enriched in detergent-resistant biomembrane fractions associated with microdomains, i.e. rafts and caveolae. Here, the lateral interactions of cholesterol with LacCers containing various homogeneous saturated (8:0, 16:0, 18:0, 24:0) or mono-unsaturated acyl chains (18:1, 24:1) have been characterized using a Langmuir-type film balance. Cholesterol-induced changes in lateral packing were assessed by measuring changes in average molecular area, i.e. area condensations, and in lateral elasticity, i.e., surface compressional moduli (C_S^-1) with emphasis on high surface pressures ( 30 mN/m) that mimic biomembrane conditions. Cholesterol most dramatically affected the lateral packing elasticity of LacCers with long saturated acyl chains at sterol mole fractions 0.3, consistent with liquid-ordered (LO) phase formation. The lateral elasticity within the LacCer-cholesterol LO-phase was much lower than that observed within pure LacCer condensed, i.e. gel, phase. The magnitude of the cholesterol-induced reduction in lateral elasticity was strongly mitigated by cis monounsaturation in the LacCer acyl chain. At identical high sterol mole fractions, higher lateral elasticity was observed within LacCer-cholesterol mixtures compared with galactosylceramide-cholesterol and sphingomyelin-cholesterol mixtures. The results show how changes to sphingolipid headgroup and acyl chain structure contribute to the modulation of lateral packing elasticity in sphingolipid-cholesterol LO-phases.

Key Words: condensing effect, glycosphingolipid, rafts, sterol, surface compressional modulus