The effect of H3O+ on membrane structure and hydrogen bonding in phospholipid bilayers

Deplazes E1, Cranfield GC2, Sarami F3, Poger D4 and Cornell B5,2

  1. Curtin University, Perth, Australia.
  2. University of Technology Sydney, Sydney, Australia.
  3. University of Western Australia, Perth, Australia.
  4. University of Queensland, Brisbane, Australia.
  5. SDx Tethered Membranes Pty. Ltd., Sydney, Australia.

The cell membrane is critical for cells to adapt to changes in pH yet we know little about the molecular mechanisms of how hydronium ions (H3O+) affect the structure of phospholipid membranes. A recent study showed changes membrane conduction and structure as a function of H3O+ concentration. To gain molecular level insight into this effect we carried out μs-long unrestrained MD simulations of phospholipid bilayers in the presence of 10 mM and 100 mM H3O+ and compared them to the same system in the absence of H3O+. Results show that in the presence of H3O+ the membrane undergoes a significant increase in bilayer thickness accompanied by a significant decrease in the area per lipid, in agreement with experimental data. Analysis of the density profiles shows that the H3O+ ions accumulate close to the hydrophobic core of the membrane where they displace water and form hydrogen bonds with the carbonyl and phosphate oxygens of the lipids. These hydrogen bonds are, on average, shorter and longer-lived than hydrogen bonds with water molecules. Thus, our simulations confirm the hypothesis that H3O+disrupts hydrogen bonding between phospholipids and that this is likely the cause of the reduced area per lipid. In addition, the layer of constrained water at the water-lipid interface known to influence membrane morphology and structure as well as proton transport appears to increase in the presence H3O+.