Molecular dynamics simulations of the fully hydrated neat dipalmitoylphosphatidylcholine (DPPC) membrane as well as DPPC membranes containing four different general anaesthetic molecules, namely chloroform, halothane, diethyl ether and enflurane, have been simulated at two different pressures, i.e., at 1 bar and 1000 bar, at the temperature of 310 K. At this temperature the model used in this study is known to be in the biologically most relevant liquid crystalline (Lα) phase. To find out which properties of the membrane might possibly be related to the molecular mechanism of anaesthesia, we have been looking for properties that change in the same way in the presence of any general anaesthetic molecule, and change in the opposite way by the increase of pressure. This way, we have ruled out the density distribution of various groups along the membrane normal axis, orientation of the lipid heads and tails, self-association of the anaesthetics, as well as the local order of the lipid tails as possible molecular reasons of anaesthesia. On the other hand, we have found that the molecular surface area, and hence also the molecular volume of the membrane, is increased by the presence of any anaesthetic molecule, and decreased by the pressure, in accordance with the more than half a century old critical volume hypothesis. We have also found that anaesthetic molecules prefer two different positions along the membrane normal axis, namely the middle of the membrane and the outer edge of the hydrocarbon region, close to the polar headgroups. The increase of pressure is found to decrease the former, and increase the latter preference, and hence it might also be related to the pressure reversal of anaesthesia.
ASJC Scopus subject areas
- Physics and Astronomy(all)
- Physical and Theoretical Chemistry