Effect of Melatonin and Cholesterol on the Structure of DOPC and DPPC Membranes

Journal Article · Tue Jan 01 00:00:00 EST 2013 · Biochimica et Biophysica Acta (BBA) - Biomembranes

DOI:https://doi.org/10.1016/j.bbamem.2013.05.015· OSTI ID:1087514

Drolle, E ^[1]; Kucerka, Norbert ^[2]; Hoopes, M I ^[1]; Choi, Y ^[1]; Katsaras, John ^[3]; Karttunen, M ^[1]; Leonenko, Z ^[1]

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1. University of Waterloo, Canada
2. Canadian Neutron Beam Centre and Comelius University (Slovakia)
3. ORNL

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 andMolecular 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-snglycero-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.

• Research Organization: Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
• Sponsoring Organization: USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE Office of Science (SC)
• DOE Contract Number: DE-AC05-00OR22725
• OSTI ID: 1087514
• Journal Information: Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1828, Issue 9; ISSN 0005-2736
• Country of Publication: United States
• Language: English