Different effects of oxysterols on a model lipid raft - Langmuir monolayer study complemented with theoretical calculations

Abstract

Three oxysterols (7β-hydroxycholesterol; 7β-OH, 7-ketocholesterol; 7-K and 25-hydroxycholesterol, 25-OH) differing in the site of oxidation (ring system versus chain) and kind of polar group (hydroxyl versus carbonyl) were studied in lipid raft environment using the Langmuir monolayer technique complemented with theoretical calculations. Experiments were performed for the unmodified raft system, composed of sphingomyelin (SM) and cholesterol (Chol), and in the next step the raft was modified by the incorporation of oxysterol in different proportions. In the examined three-component system (Chol:SM:oxysterol), apart from interactions between the lipid raft components, the affinity of Chol to its oxidized derivatives also plays an important role. 25-OH was found to enhance interactions between SM and Chol and thus stabilize the raft, contrary to 7β-OH and 7-K, which exerted the fluidizing effect as well as the destabilization of the raft. Different action of oxysterols on model raft was observed. 7β-OH and 7-K, which are highly potent inducers of cell death caused raft destabilization, while 25-OH, which is the least toxic of the investigated oxysterols, was found to stabilize the raft.

Keywords: Langmuir monolayer; Lipid domains; Membrane model; Molecular dynamic; Oxysterols.