Effect of xenon, an apolar general anaesthetic on the properties of the DPPC bilayer

0574259 - ÚOCHB 2024 RIV NL eng J - Journal Article
Rozsa, Z. B. - Fábián, Balázs - Hantal, G. - Szöri, M. - Jedlovszky, P.
Effect of xenon, an apolar general anaesthetic on the properties of the DPPC bilayer.
Journal of Molecular Liquids. Roč. 386, September (2023), č. článku 122405. ISSN 0167-7322. E-ISSN 1873-3166
Institutional support: RVO:61388963
Keywords : general anesthesia * xenon * DPPC bilayer * molecular dynamics simulation * pressure reversal * critical surface area hypothesis
OECD category: Physical chemistry
Impact factor: 6, year: 2022
Method of publishing: Open access
https://doi.org/10.1016/j.molliq.2023.122405

The effect of xenon, a general anaesthetic, on the properties of the fully hydrated dipalmitoylphosphatidylcholine (DPPC) bilayer is investigated by molecular dynamics simulations with two different force fields. Considering the well-known pressure reversal of the anaesthetic effect, we are looking for such changes that are reverted by the increase of the pressure, and hence can be relevant in explaining the molecular mechanism of general anesthesia. The results show that, besides its main preference for staying in the middle of the membrane, xenon also has a secondary preference for positions at the outer boundary of the hydrocarbon region, close to the crowded domain of the polar headgroups. This outer preference is a result of the interplay of the increasing attraction the xenon atoms experience and the decreasing free volume available for them upon going away from the middle of the membrane. It also turns out that any change that might be relevant in explaining the anaesthetic effect is related to xenon atoms staying in this outer preferred position. Since the model we employed does not account for the polarizability of the xenon atoms, and hence misses a part of the thermodynamic driving force of the preference for this outer position, all results should be considered as a lower bound estimate of the real effect. It is found that the xenon atoms induce a lateral swelling of the membrane by pushing the DPPC molecules farther away from each other, which, due to the insensitivity of the membrane thickness to the presence of xenon, naturally results in an increase of also the membrane volume. On the other hand, pressure increases the membrane thickness by increasing the order of the lipid tails, while it also causes a lateral shrinking of the bilayer. The net effect of these two opposite contributions is still a decrease of the membrane volume. In the light of these results, we propose to refine the 70 years old 'critical volume hypothesis' to a 'critical surface area hypothesis', claiming that general anesthesia occurs if the molar surface area of the membrane exceeds a critical value. Finally, the xenon-induced lateral swelling results in an increase of the empty space in the hydrocarbon region, allowing the DPPC molecules to move more freely, and hence increasing their lateral diffusion coefficient. All these changes are clearly reverted by pressure, and thus may well be relevant in respect of the molecular mechanism of general anesthesia.
Permanent Link: https://hdl.handle.net/11104/0344601