Abstract
Phospholipids with unsaturated acyl chains are major targets of reactive oxygen species leading to formation of oxidized lipids. Oxidized phospholipids have a pronounced role in cell membrane damage. We investigated the effect of oxidation on physiological properties of phospholipid bilayers using atomistic molecular dynamics simulations. We studied phospholipid bilayer systems of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and its two stable oxidized products, 1-palmitoyl-2-(9′-oxo-nonanoyl)-sn-glycero-3-phosphocholine (PoxnoPC) and 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PazePC). Structural properties of the POPC lipid bilayer upon the addition of PoxnoPC or PazePC with concentration ranging from 10% to 30% were described. The key finding is that PazePC lipids bend their polar tails toward the bilayer-water interface whereas PoxnoPC lipids orient their tail toward the bilayer interior. The bilayer thickness decreases such that the thickness reduction in bilayers containing PazePC is stronger than in bilayers containing PoxnoPC. The average area per lipid decreases with a stronger effect in bilayers containing PoxnoPC. The addition of PoxnoPC makes both POPC acyl chains slightly more ordered whereas the addition of PazePC reduces the order in the two POPC acyl chains. These structural changes lead to an enhancement in the permeabilities of the bilayers containing these two oxidized products depending on the type, and the amount of oxidation. This enhancement can be achieved with a lower concentration of PazePC (10% or 15%), whereas a higher concentration of PoxnoPC (20%) is required to achieve an apparent enhancement in permeability. While the permeability of bilayers containing PazePC is higher than bilayers containing PoxnoPC in the 10-20% concentration range, by increasing the concentration of the oxidized products to higher than 20%, permeability of the bilayers containing PazePC is reduced such that it is slightly smaller than those containing PoxnoPC.
| Original language | English |
|---|---|
| Pages (from-to) | 18310–18321 |
| Number of pages | 12 |
| Journal | Physical Chemistry Chemical Physics |
| Volume | 25 |
| Issue number | 27 |
| DOIs | |
| Publication status | Published - 12 Jul 2023 |
Bibliographical note
Funding Information:The authors thank Antoinette Killian, Joseph Lorent, and Min Xie from the University of Utrecht for many fruitful discussions. BB thanks Björn Baumeier at the Technical University of Eindhoven (TU/e) for providing computational resources and the strategic alliance between TU/e, Utrecht University, and University Medical Center Utrecht for financial support. MK thanks the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Canada Research Chairs Program for financial support. J. W. was financially supported by National Research Council of Thailand (NRCT) through the Research Grants for Talented Mid-Career Researchers with grant no. N41A640080.
Publisher Copyright:
© 2023 The Royal Society of Chemistry.