Comparative molecular dynamics study of ether- and ester-linked phospholipid bilayers

Abstract

The lipid membranes found in archaea have high bilayer stability and low permeability. The molecular structure of their constituent lipids is characterized by ether-linked, branched hydrophobic chains, whereas the conventional lipids obtained from eukaryotic or eubacterial sources have ester linked straight chains. In order to elucidate the influence of the ether linkage, instead of an ester one, on the physical properties of the lipid bilayers, we have carried out comparative 10 ns molecular dynamics simulations of diphytanyl phosphatidylcholine (ether-DPhPC) and diphytanoyl phosphatidylcholine (ester-DPhPC) bilayers in water, respectively. We analyze bilayer structures, hydration of the lipids, membrane dipole potentials, and free energy profiles of water and oxygen across the bilayers. We observe that the membrane dipole potential for the ether-DPhPC bilayer, which arises mainly from the ether linkage, is about half of that of the ester-DPhPC. The calculated free energy barrier for a water molecule in the ether-DPhPC bilayer system is slightly higher than that in the ester-DPhPC counterpart, which is in accord with experimental data.

On the Electroporation Thresholds of Lipid Bilayers: Molecular Dynamics Simulation Investigations

“…The areas per molecule for the DPhPC-ester and DPhPC-ether bilayers slightly change in the absence of salt and as the temperature is further lowered to 25°C (Table 1). At 25°C the values found here for DPhPC-ester and DPhPC-ether (78.6 ± 0.6 and 73.6 ± 0.4 Å 2 ) match quite nicely those reported by others (Shinoda et al 2004a) (77.7 and 74.1 Å 2 ). Finally, as a comparison, the experimentally determined area per molecule for DPhPC-ester is 76 Å 2 (Wu et al 1995), which provides some confidence in the force field and protocol used here.…”

“…DPhPC-ester and DPhPC-ether are not described in this force field topology database; the former was therefore built by adding four methyl groups to each tail of DPPC lipid, while the latter was subsequently built by changing the ester bond to an ether bond in the DPhPC-ester molecules. The force field parameters of ether linkage were adopted from Shinoda et al (2004a).…”

“…The difference in ester and ether linkage affects, on the other hand, the headgroup hydration and the membrane electrostatic potential. DPhPC-ester bilayers, for instance, have a dipole potential two times larger than DPhPC-ether bilayers (Shinoda et al 2004a). We may therefore expect a direct effect on the stability of such bilayers under electrical stress, i.e., exposure to an electric field.…”

A Quantitative Coarse-Grain Model for Lipid Bilayers

“…The choice of a 2 fs time step in the AL run is typical for AL membrane simulations. 19,[26][27][28][29][30][31][32][34][35][36] We are aware that the use of constraint and multistep algorithms can allow time steps of 4 21,22 and even 5 fs, 20,23 hence more than twice larger than that employed in our test. Using a 5 fs time step in the AL run would bring the CG speed-up factor down to ≈50.…”

Recent development in computer simulations of lipid bilayers

“…Studies of the gel to liquid-crystal phase transitions of fully hydrated bilayers were also performed 147,149,150 . It should be mentioned also a series of MD simulations of the specific branch-chained lipid bilayers [151][152][153][154][155] and a ceramide bilayer [156][157][158] .…”