Atomic-Scale Structure and Electrostatics of Anionic Palmitoyloleoylphosphatidylglycerol Lipid Bilayers with Na+ Counterions

Abstract

Anionic palmitoyloleoylphosphatidylglycerol (POPG) is one of the most abundant lipids in nature, yet its atomic-scale properties have not received significant attention. Here we report extensive 150-ns molecular dynamics simulations of a pure POPG lipid membrane with sodium counterions. It turns out that the average area per lipid of the POPG bilayer under physiological conditions is approximately 19% smaller than that of a bilayer built from its zwitterionic phosphatidylcholine analog, palmitoyloleoylphosphatidylcholine. This suggests that there are strong attractive interactions between anionic POPG lipids, which overcome the electrostatic repulsion between negative charges of PG headgroups. We demonstrate that interlipid counterion bridges and strong intra- and intermolecular hydrogen bonding play a key role in this seemingly counterintuitive behavior. In particular, the substantial strength and stability of ion-mediated binding between anionic lipid headgroups leads to complexation of PG molecules and ions and formation of large PG-ion clusters that act in a concerted manner. The ion-mediated binding seems to provide a possible molecular-level explanation for the low permeability of PG-containing bacterial membranes to organic solvents: highly polar interactions at the water/membrane interface are able to create a high free energy barrier for hydrophobic molecules such as benzene.

Ion Dynamics in Cationic Lipid Bilayer Systems in Saline Solutions

“…In particular, it has been demonstrated that cations (e.g., Na + ions) are able to penetrate rather deep in the lipid headgroup region. This effect has been observed in zwitterionic, 33,42,46,[50][51][52][53] anionic, 55,56,58 and slightly cationic 61 lipid bilayers. The findings agree with experimental data.…”

“…[28][29][30][31][32][33][34][35][36][37][38][39][40][41] As for molecular-level computational studies, the increase in computing power in the past few years has made it possible to extend computer simulations beyond the relatively long relaxation times of tens to hundreds of nanoseconds required for equilibration of ions in lipid/water systems. Although most computational studies by far have focused on the effects of salt ions on zwitterionic (neutral) lipid bilayers, 33,[42][43][44][45][46][47][48][49][50][51][52][53] there is also an increasing number of studies on anionic [54][55][56][57][58][59] and cationic 60,61 lipid bilayers. Most simulations have addressed the effect of ions on the structural and electrostatic properties of lipid membranes.…”

Ionic Surfactant Aggregates in Saline Solutions: Sodium Dodecyl Sulfate (SDS) in the Presence of Excess Sodium Chloride (NaCl) or Calcium Chloride (CaCl2)

“…89,90,67 Ion condensation, however, depends strongly on geometry. 91 Reference 89 reports that sodium ions affect both the structure and dynamics of a lipid bilayer.…”

Membrane Perturbation Action Mode and Structure-Activity Relationships of Protonectin, a Novel Antimicrobial Peptide from the Venom of the Neotropical Social Wasp Agelaia pallipes pallipes

“…Protonectin and its proline-substituted analogs were synthesized by a stepwise solid-phase method using N-9-fluorenylmethoxycarbonyl (F-moc) chemistry (7). The peptides were purified on a Sephadex gel column and by reverse-phase high-performance liquid chromatography (HPLC) (Waters) using a -Bondapak C 18 19-mm by 300-mm column with gradient elution of 20% to 75% CH 3 CN/H 2 O with 0.1% trifluoroacetic acid (TFA) at a flow rate of 8 ml/min. The atomic mass of the synthetic peptides was confirmed by electrospray ionizationmass spectrometry (ESI-MS).…”

“…The simple point charge (SPC) model (15,16) was used for water, and water geometry was constrained with the SETTLE algorithm (17). POPC parameters were previously reported (18,19). A Berendsen thermostat with a coupling constant of 0.2 ps was applied in all simulations.…”