Oxysterols are products of cholesterol oxidation. They can be formed endogenously (in both enzymatic and non-enzymatic reactions) as well as exogenously (delivered with food). Recent studies clearly demonstrate cytotoxic properties of these compounds, being mainly due to their incorporation into natural lipid bilayers. This process can influence mechanical and physicochemical properties of biomembrane—mainly by modifying the interactions between its components, which may result in the disruption of proper functioning of cell membrane and could lead to its degradation. Therefore, it can be assumed that oxysterols may affect the initiation of neurodegenerative diseases, including Alzheimer’s disease. However, the mode of action of these molecules at the molecular level is not fully known. To get a better understanding of the role of oxysterols in neurodegeneration, it is of great importance to examine mutual interactions between oxysterols and neuronal membrane components. One of the most promising techniques that can be used to analyze such interactions is the Langmuir monolayer technique. In this work, we have prepared an artificial neuronal membrane modeled as multicomponent Langmuir monolayer built up with cholesterol, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and sphingomyelin (SM). To examine whether there are any changes in the membrane properties under oxidative stress, in this paper we have investigated the impact of the representative ring-oxidized oxysterol: 7-ketocholesterol (7-KC). Our results show that replacing cholesterol with 7-KC increases the interaction between molecules in the model membrane.Electronic supplementary materialThe online version of this article (doi:10.1007/s00232-017-9984-8) contains supplementary material, which is available to authorized users.
In this paper, a representative of chain-oxidized sterols, 25-hydroxycholesterol (25-OH), has been studied in Langmuir monolayers mixed with the sphingolipids sphingomyelin (SM) and ganglioside (GM
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) to build lipid rafts. A classical Langmuir monolayer approach based on thermodynamic analysis of interactions was complemented with microscopic visualization of films (Brewster angle microscopy), surface-sensitive spectroscopy (polarization modulation–infrared reflection–absorption spectroscopy) and theoretical calculations (density functional theory modelling and molecular dynamics simulations). Strong interactions between 25-OH and both investigated sphingolipids enabled the formation of surface complexes. As known from previous studies, 25-OH in pure monolayers can be anchored to the water surface with a hydroxyl group at either C(3) or C(25). In this study, we investigated how the presence of additional strong interactions with sphingolipids modifies the surface arrangement of 25-OH. Results have shown that, in the 25-OH/GM
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system, there are no preferences regarding the orientation of the 25-OH molecule in surface complexes and two types of complexes are formed. On the other hand, SM enforces one specific orientation of 25-OH: being anchored with the C(3)–OH group to the water. The strength of interactions between the studied sphingolipids and 25-OH versus cholesterol is similar, which indicates that cholesterol may well be replaced by oxysterol in the lipid raft system. In this way, the composition of lipid rafts can be modified, changing their rheological properties and, as a consequence, influencing their proper functioning.
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