Effect of xenon, an apolar general anaesthetic on the properties of the DPPC bilayer
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00574259" target="_blank" >RIV/61388963:_____/23:00574259 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1016/j.molliq.2023.122405" target="_blank" >https://doi.org/10.1016/j.molliq.2023.122405</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.molliq.2023.122405" target="_blank" >10.1016/j.molliq.2023.122405</a>
Alternative languages
Result language
angličtina
Original language name
Effect of xenon, an apolar general anaesthetic on the properties of the DPPC bilayer
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10403 - Physical chemistry
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Molecular Liquids
ISSN
0167-7322
e-ISSN
1873-3166
Volume of the periodical
386
Issue of the periodical within the volume
September
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
9
Pages from-to
122405
UT code for WoS article
001032037300001
EID of the result in the Scopus database
2-s2.0-85163473045