Melatonin Counteracts Cholesterol's Effects on Lipid Membrane Structure

Abstract

The cell membrane plays an important role in amyloid toxicity in relation to Alzheimer's disease. The membrane's composition and the inclusion of small molecules, such as melatonin and cholesterol, may alter the membrane's structure and physical properties, affecting its interaction with amyloid peptides. Both melatonin and cholesterol have been linked to amyloid toxicity. Melatonin has been shown to have a protective role against amyloid toxicity, while the underlying molecular mechanism of this protection is still not well understood. Here we have studied the non-specific interaction of melatonin and cholesterol with a model lipid membrane. We used small-angle neutron diffraction (SAND) from oriented lipid multilayers and small-angle neutron scattering (SANS) from unilamellar vesicles experiments to elucidate the structure of DOPC and DPPC model membrane in order to determine the effects of melatonin and cholesterol. From the present study we conclude that cholesterol and melatonin affect the lipid membrane differentially. Specifically, the incorporation of melatonin results in membrane thinning, in stark contrast to the increase in membrane thickness induced by cholesterol. This very different response of membrane thickness to cholesterol and melatonin may help to understand their relation to amyloid toxicity.