N- and O-methylation of sphingomyelin markedly affects its membrane properties and interactions with cholesterol

6533b822fe1ef96bd127cdac

RESEARCH PRODUCT

N- and O-methylation of sphingomyelin markedly affects its membrane properties and interactions with cholesterol

Anders Björkbom Tomasz Róg Tomasz Róg Thomas K.m. Nyholm Ilpo Vattulainen Ilpo Vattulainen Ilpo Vattulainen Shigeo Katsumura Lassi Paavolainen Shishir Jaikishan J. Peter Slotte Joacim Päivärinne Karol Kaszuba Pasi Kankaanpää Tetsuya Yamamoto Daniel Lindroos Mayuko Kurita Shou Yamaguchi

subject

Hydrogen bonding Lipid Bilayers Biophysics Sterol partitioning Methylation Biochemistry Membrane Lipids chemistry.chemical_compound Amide Molecular dynamics simulation Organic chemistry Molecule Acyl chain order Molecular Structure Hydrogen bond Chemistry Vesicle Bilayer Temperature ta1182 Methylation Cell Biology Sphingomyelins Kinetics Sterols Cholesterol Membrane Lateral domains Biophysics Anisotropy Sphingomyelin

description

We have prepared palmitoyl sphingomyelin (PSM) analogs in which either the 2-NH was methylated to NMe, the 3-OH was methylated to OMe, or both were methylated simultaneously. The aim of the study was to determine how such modifications in the membrane interfacial region of the molecules affected interlipid interactions in bilayer membranes. Measuring DPH anisotropy in vesicle membranes prepared from the SM analogs, we observed that methylation decreased gel-phase stability and increased fluid phase disorder, when compared to PSM. Methylation of the 2-NH had the largest effect on gel-phase instability (T(m), was lowered by similar to 7 degrees C). Atomistic molecular dynamics simulations showed that fluid phase bilayers with methylated SM analogs were more expanded but thinner compared to PSM bilayers. It was further revealed that 3-OH methylation dramatically attenuated hydrogen bonding also via the amide nitrogen, whereas 2-NH methylation did not similarly affect hydrogen bonding via the 3-OH. The interactions of sterols with the methylated SM analogs were markedly affected. 3-OH methylation almost completely eliminated the capacity of the SM analog to form sterol-enriched ordered domains, whereas the 2-NH methylated SM analog formed sterol-enriched domains but these were less thermostable (and thus less ordered) than the domains formed by PSM. Cholestatrienol affinity to bilayers containing methylated SM analogs was also markedly reduced as compared to its affinity for bilayers containing PSM. Molecular dynamics simulations revealed further that cholesterol's bilayer location was deeper in PSM bilayers as compared to the location in bilayers made from methylated SM analogs. This study shows that the interfacial properties of SMs are very important for interlipid interactions and the formation of laterally ordered domains in complex bilayers. (C) 2011 Elsevier B.V. All rights reserved.

year	journal	country	edition	language
2011-04-01	Biochimica et Biophysica Acta (BBA) - Biomembranes

10.1016/j.bbamem.2011.01.009 http://dx.doi.org/10.1016/j.bbamem.2011.01.009