The effects of oxidised phospholipids and cholesterol on the biophysical properties of POPC bilayers

Abstract

Oxidation of unsaturated membrane phospholipids by oxidative stress is associated with inflammation, infection, numerous diseases and neurodegenerative disorders. Lipid oxidation is observed in experimental samples when the parent lipid is exposed to oxidative stressors. The effect of phospholipid oxidation on the properties of biological membranes are still being explored, while low concentrations (0.1-2.0 mol%) of oxidised phospholipids are associated with disease states [1]. Previous computational studies have focused on the effect of high concentrations (~50 mol%) of oxidised phospholipids on binary lipid bilayers. This work systematically characterises the effect of lower concentrations (~10 mol%) of two oxidised lipid species, PoxnoPC (1-palmitoyl-2-(9'-oxo-nonanoyl)-sn-glycero-3-phosphocholine) or PazePC (1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine), on POPC/cholesterol and pure POPC bilayers. During μs atomistic simulations in pure POPC bilayers, PoxnoPC and PazePC reoriented their oxidised sn-2 acyl chains towards the solution, and PazePC adopted an extended conformation. The addition of 20 mol% cholesterol not only modulated the fluidity of the bilayers; it also modulated the flexibility of the PoxnoPC oxidised sn-2 tail, reducing bilayer disorder. In contrast, the addition of cholesterol had little effect on bilayers containing PazePC. Our studies show that the effect of oxidised lipids on the biophysical properties of a multicomponent bilayer cannot be intuitively extrapolated from a binary lipid system.

Amyloid β Dodecamer Disrupts the Neuronal Membrane More Strongly than the Mature Fibril: Understanding the Role of Oligomers in Neurotoxicity

“… 81 Our A value is reasonable as it is close to 53.0 ± 0.7 Å 2 of the POPC/cholesterol (80:20) membrane with a cholesterol ratio similar to our model (18%). 83 …”

Role of Oxidized Lipids in Permeation of H2O2 Through a Lipid Membrane: Molecular Mechanism of an Inhibitor to Promoter Switch

“…Such a large change in A ox-lipid can be explained by a change in the molecular configuration of POVPC in the DOPC bilayer. Previous reports based on molecular dynamic simulations proved that hydrophilic aldehyde group tends to escape from a hydrophobic alkyl region to a hydrophilic head group region by the intra-molecular configuration change 27,28,32,33 . Since such looped structure increases the molecular area occupied by the oxidized lipid, the increased A ox-lipid at 10 mol % can be interpreted in terms of the formation of the looped structure.…”

“…Concerning passive permeation through cell membranes, an influence of the oxidized lipid has also been investigated by both experiments and simulations 29,30,32,39–41 , especially focusing on its effect on intra-molecular and an inter-molecular structural changes. The former involves the reorientation of the oxidized tails ( sn -2 acyl chains) toward the water/membrane interface to form hydrogen bonds with water and the polar headgroup of surrounding lipids 27,28,32,33 . The reorientation angle between the vector from the first carbon to the oxidized carbon and the normal bilayer has been calculated to be in the range of 96–118 ° for both shorter and longer oxidized carbon chains, indicating that most oxidized tails prefer to undergo intra-molecular reorientation and form a looped structure by bending their oxidized moiety toward the water/membrane interface 27 .…”

Is natural fraxin an overlooked radical scavenger?

“…Thus, this bond was used to calculate the pK a of FX. The pK a was computed following the literature, 22,64 the molar fractions (% A À and % HA) were computed following eqn (12) and the results are shown in Fig. 3.…”

“…Recent studies showed that radical reactions could be modeled with high accuracy using quantum chemical methods and a combination of thermodynamic and kinetic modeling. [9][10][11][12][13] This approach provides an efficient and practical protocol to screen the antioxidant activity of natural products in silico with high accuracy; this is particularly useful for evaluating the activity in physiological environments. 10,14 The computational method was successfully applied to investigate the antioxidant activity of numerous organic compounds.…”