The structure of the zwitterionic headgroups in a DMPC bilayer as seen from Monte Carlo simulation: Comparisons with ionic solutions

The ionic structure of the headgroup region of a fully hydrated dimyristoylphosphatidylcholine (DMPC) bilayer is analysed on the basis of an all-atom Monte Carlo simulation. Similar analyses are also performed on simulated configurations of 2 M aqueous o-phosphorylcholine (o-PC), and 1 M, 2 M and 3 M aqueous tetramethylammonium-dimethylphosphate (TA-DP) solutions as reference systems. These homogeneous solutions contain the same ionic groups as the zwitterionic headgroup of the DMPC molecule, in the form of zwitterions and free ions, respectively. The potential of mean force acting between the pairs of these ions in water is also determined. It is found that the distribution of the tetramethylammonium (TA) and dimethylphosphate (DP) ionic groups is very similar in the headgroup region of the DMPC membrane to that in the homogeneous zwitterionic o-PC solution. The analysis of the potential of mean force acting between the different ion pairs in infinitely dilute aqueous solution reveals that the free energy of the formation of a contact TA or a solvent-shared DP ion pair is considerably lower than that of a contact TA-DP ion pair, due to the marked difference in the hydrophobicity of these two ions. Although this effect does not affect noticeably the structure of the TA-DP solutions investigated, it results in an unusual behaviour of the ionic groups in the systems containing zwitterions (i.e., preferential parallel alignment of the neighbouring zwitterions, contact TA-TA pair formation) that is fully in accordance with the constraints imposed by the amphiphilic structure of the lipid bilayer. This fact can explain the stability of the membranes consisting of phosphatidylcholine lipid molecules and the prevalence of these kinds of molecules among the constituents of the membrane of living cells.