Acyl Chain Disorder and Azelaoyl Orientation in Lipid Membranes Containing Oxidized Lipids.
Oxidized phospholipids occur naturally in conditions of oxidative stress and have been suggested to play an important role in a number of pathological conditions due to their effects on a lipid membrane acyl chain orientation, ordering, and permeability. Here we investigate the effect of the oxidized phospholipid 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PazePC) on a model membrane of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) using a combination of (13)C-(1)H dipolar-recoupling nuclear magnetic resonance (NMR) experiments and united-atom molecular dynamics (MD) simulations. The obtained experimental order parameter SCH profiles show that the presence of 30 mol % PazePC in the bilayer significantly increases the gauche content of the POPC acyl chains, therefore decreasing the thickness of the bilayer, although with no stable bilayer pore formation. The MD simulations reproduce the disordering effect and indicate that the orientation of the azelaoyl chain is highly dependent on its protonation state with acyl chain reversal for fully deprotonated states and a parallel orientation along the interfacial plane for fully protonated states, deprotonated and protonated azelaoyl chains having negative and positive SCH profiles, respectively. Only fully or nearly fully protonated azelaoyl chain are observed in the (13)C-(1)H dipolar-recoupling NMR experiments. The experiments show positive SCH values for the azelaoyl segments confirming for the first time that oxidized chains with polar termini adopt a parallel orientation to the bilayer plane as predicted in MD simulations.
Institut für Physik - NMR, Martin-Luther-Universität Halle-Wittenberg , 06108 Halle, Germany.
Tiago
T
Mendes Ferreira
Department of Neuroscience and Biomedical Engineering, Aalto University , 02150 Espoo, Finland.
Rohit
R
Sood
Institut für Physik - NMR, Martin-Luther-Universität Halle-Wittenberg , 06108 Halle, Germany.
Ruth
R
Bärenwald
Centre for Analysis and Synthesis, Lund University , SE-221 00 Lund, Sweden.
Göran
G
Carlström
Physical Chemistry, Lund University , SE-221 00 Lund, Sweden.
Daniel
D
Topgaard
Institut für Physik - NMR, Martin-Luther-Universität Halle-Wittenberg , 06108 Halle, Germany.
Kay
K
Saalwächter
Department of Neuroscience and Biomedical Engineering, Aalto University , 02150 Espoo, Finland.
Paavo K J
PK
Kinnunen
Department of Neuroscience and Biomedical Engineering, Aalto University , 02150 Espoo, Finland.
O H Samuli
OH
Ollila
D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000737:chemistry*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000737:chemistry
C528536:1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010767:Phosphorylcholine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine