Reflectometry and molecular dynamics study of the impact of cholesterol and melatonin on model lipid membranes

The effect of melatonin and/or cholesterol on the structural properties of a model lipid bilayer prepared from 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) has been investigated both experimentally and via molecular dynamics (MD) simulations. Neutron reflectometry experiments performed with single supported membranes revealed changes in lipid bilayer thickness upon the introduction of additional components. While the presence of cholesterol led to an increase in membrane thickness, the opposite effect was observed in the case of melatonin. The results obtained are in a good agreement with MD simulations which provided further information on the organization of components within the systems examined, indicating a mechanism underlying the membranes' thickness changes due to cholesterol and melatonin that had been observed experimentally. Cholesterol and melatonin preferentially accumulate in different membrane regions, presumably affecting the conformation of lipid hydrophobic moieties differently, and in turn having distinct impacts on the structure of the entire membrane. Our findings may be relevant for understanding the effects of age-related changes in cholesterol and melatonin concentrations, including those in the brains of individuals with Alzheimer's disease.