Molecular insight into neurodegeneration – Langmuir monolayer study on the influence of oxysterols on model myelin sheath

Abstract

Systematic studies on the influence of selected ring–oxidized (7α–hydroxycholesterol, 7α−OH; 7β–hydroxycholesterol, 7β−OH; 7–ketocholesterol, 7–K) and chain–oxidized (25−OH) sterols on lipid layer of myelin were performed. Myelin sheath was modeled as five–component Langmuir monolayer (Chol:PE:SM:PS:PC 50:20:12:9:9). Particular oxysterols have been incorporated into the model myelin sheath by replacing cholesterol totally or partially (1:1). The effect of oxysterol incorporation was characterized with surface pressure and electric surface potential – area isotherms and visualized with Brewster angle microscopy (BAM) and atomic force microscopy (AFM). It has been noticed that model myelin loses its homogeneous structure (due to the appearance of domains) at physiological bilayer conditions (30–35 mN/m). In the presence of oxysterols, the fluidity of myelin model increases and the organization of lipids is altered, which is reflected in the decrease of electric surface potential changes (ΔV). The strongest myelin/oxysterol interactions have been observed for 7–K and 25−OH, being the most cytotoxic oxysterols found in biological tests.