Cholesterol and melatonin regulated membrane fluidity does not affect the membrane breakage triggered by amyloid-beta peptide.

We have studied by means of small angle neutron scattering and diffraction, and molecular dynamics simulations the effect of lipid membrane fluidity on the amyloid-beta peptide interactions with the membrane. These interactions have been discovered previously to trigger the reorganization of model membranes between unilamellar vesicles and planar membranes (bicelle-like structures) during the lipid phase transition. The morphology changes were taking place in rigid membranes prepared of fully saturated lipids and were proposed to play a role in the onset of amyloid related disorders. We show in this study that the replacement of fully saturated lipids by more fluid mono-unsaturated lipids eliminates the mentioned morphology changes, most likely due to the absence of phase transition within the temperature range investigated. We have therefore controlled the membrane rigidity also while ensuring the presence of membrane phase transition within the biologically relevant temperatures. It was done by the addition of melatonin and/or cholesterol to the initial membranes made of saturated lipids. Small angle neutron scattering experiments performed over a range of cholesterol and melatonin concentrations show their distinctive effects on the local membrane structure only. The cholesterol for example affects the membrane curvature such that spontaneously formed unilamellar vesicles are of much larger sizes than those formed by the neat lipid membranes or membranes with melatonin added. The temperature dependent experiments, however, reveal no influence on the previously discovered membrane breakage whether cholesterol or melatonin have been added.

Application of small-angle neutron diffraction to the localization of general anesthetics in model membranes.

We set out to explore the applicability of small-angle neutron diffraction (SAND) to the localization of biomembrane components by studying the general anesthetic n-decane in a model lipid bilayer system composed of dioleoyl-phosphocholine (DOPC). Samples in the form of planar membrane multilayers were hydrated by varied mixtures of deuterated and protonated water, and examined by the means of SAND. Neutron scattering length density (NSLD) profiles of the system were then reconstructed from the experimental data. We exploited the significantly different neutron scattering properties of hydrogen and deuterium atoms via labeling in addition to water contrast variation. Enhancing the signals from particular components of bilayer system led to a set of characteristic membrane profiles and from their comparison we localized n-decane molecules unequivocally in the bilayer's hydrocarbon chain region.