Effect of melatonin and cholesterol on the structure of DOPC and DPPC membranes

• Published in: Biochimica et biophysica acta 2013-09, Vol.1828 (9), p.2247-2254
• Main Authors: Drolle, E., Kučerka, N., Hoopes, M.I., Choi, Y., Katsaras, J., Karttunen, M., Leonenko, Z.
• Format: Article
• Language: English
• Subjects: Amyloid - chemistry; Cholesterol; Cholesterol - chemistry; Lipid membrane; Melatonin; Melatonin - chemistry; Membrane Fluidity; Molecular Dynamics Simulation; Molecular Dynamics simulations; Neutron Diffraction; Phosphatidylcholines - chemistry; Phosphorylcholine - analogs & derivatives; Phosphorylcholine - chemistry; Scattering, Small Angle; Small-angle neutron diffraction (SAND); Small-angle neutron scattering (SANS); Unilamellar Liposomes - chemistry
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/j.bbamem.2013.05.015

The cell membrane plays an important role in the molecular mechanism of amyloid toxicity associated with Alzheimer's disease. The membrane's chemical composition and the incorporation of small molecules, such as melatonin and cholesterol, can alter its structure and physical properties, thereby affecting its interaction with amyloid peptides. Both melatonin and cholesterol have been recently linked to amyloid toxicity. Melatonin has been shown to have a protective role against amyloid toxicity. However, the underlying molecular mechanism of this protection is still not well understood, and cholesterol's role remains controversial. We used small-angle neutron diffraction (SAND) from oriented lipid multi-layers, small-angle neutron scattering (SANS) from unilamellar vesicles experiments and Molecular Dynamics (MD) simulations to elucidate non-specific interactions of melatonin and cholesterol with 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) model membranes. We conclude that melatonin decreases the thickness of both model membranes by disordering the lipid hydrocarbon chains, thus increasing membrane fluidity. This result is in stark contrast to the much accepted ordering effect induced by cholesterol, which causes membranes to thicken. [Display omitted] •Inclusion of melatonin and cholesterol can alter structure and function of biomembrane.•We studied non-specific interaction of melatonin and cholesterol with DOPC and DPPC membranes.•We used small-angle neutron diffraction (SAND), small-angle neutron scattering (SANS) and Molecular Dynamics simulations.•Melatonin decreases thickness of both model membranes and increases the area per lipid by inducing disorder in lipid tails.•This is opposite to the effect of cholesterol, which increases the thickness of both membranes.