Understanding the Molecular Mechanism of Anesthesia: Effect of General Anesthetics and Structurally Similar Non-Anesthetics on the Properties of Lipid Membranes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00573774" target="_blank" >RIV/61388963:_____/23:00573774 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1021/acs.jpcb.3c02976" target="_blank" >https://doi.org/10.1021/acs.jpcb.3c02976</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jpcb.3c02976" target="_blank" >10.1021/acs.jpcb.3c02976</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Understanding the Molecular Mechanism of Anesthesia: Effect of General Anesthetics and Structurally Similar Non-Anesthetics on the Properties of Lipid Membranes

Popis výsledku v původním jazyce

General anesthesia can be caused by various, chemically very different molecules, while several other molecules, many of which are structurally rather similar to them, do not exhibit anesthetic effects at all. To understand the origin of this difference and shed some light on the molecular mechanism of general anesthesia, we report here molecular dynamics simulations of the neat dipalmitoylphosphatidylcholine (DPPC) membrane as well as DPPC membranes containing the anesthetics diethyl ether and chloroform and the structurally similar non-anesthetics n-pentane and carbon tetrachloride, respectively. To also account for the pressure reversal of anesthesia, these simulations are performed both at 1 bar and at 600 bar. Our results indicate that all solutes considered prefer to stay both in the middle of the membrane and close to the boundary of the hydrocarbon domain, at the vicinity of the crowded region of the polar headgroups. However, this latter preference is considerably stronger for the (weakly polar) anesthetics than for the (apolar) non-anesthetics. Anesthetics staying in this outer preferred position increase the lateral separation between the lipid molecules, giving rise to a decrease of the lateral density. The lower lateral density leads to an increased mobility of the DPPC molecules, a decreased order of their tails, an increase of the free volume around this outer preferred position, and a decrease of the lateral pressure at the hydrocarbon side of the apolar/polar interface, a change that might well be in a causal relation with the occurrence of the anesthetic effect. All these changes are clearly reverted by the increase of pressure. Furthermore, non-anesthetics occur in this outer preferred position in a considerably smaller concentration and hence either induce such changes in a much weaker form or do not induce them at all.

Název v anglickém jazyce

Understanding the Molecular Mechanism of Anesthesia: Effect of General Anesthetics and Structurally Similar Non-Anesthetics on the Properties of Lipid Membranes

Popis výsledku anglicky

General anesthesia can be caused by various, chemically very different molecules, while several other molecules, many of which are structurally rather similar to them, do not exhibit anesthetic effects at all. To understand the origin of this difference and shed some light on the molecular mechanism of general anesthesia, we report here molecular dynamics simulations of the neat dipalmitoylphosphatidylcholine (DPPC) membrane as well as DPPC membranes containing the anesthetics diethyl ether and chloroform and the structurally similar non-anesthetics n-pentane and carbon tetrachloride, respectively. To also account for the pressure reversal of anesthesia, these simulations are performed both at 1 bar and at 600 bar. Our results indicate that all solutes considered prefer to stay both in the middle of the membrane and close to the boundary of the hydrocarbon domain, at the vicinity of the crowded region of the polar headgroups. However, this latter preference is considerably stronger for the (weakly polar) anesthetics than for the (apolar) non-anesthetics. Anesthetics staying in this outer preferred position increase the lateral separation between the lipid molecules, giving rise to a decrease of the lateral density. The lower lateral density leads to an increased mobility of the DPPC molecules, a decreased order of their tails, an increase of the free volume around this outer preferred position, and a decrease of the lateral pressure at the hydrocarbon side of the apolar/polar interface, a change that might well be in a causal relation with the occurrence of the anesthetic effect. All these changes are clearly reverted by the increase of pressure. Furthermore, non-anesthetics occur in this outer preferred position in a considerably smaller concentration and hence either induce such changes in a much weaker form or do not induce them at all.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Physical Chemistry B

ISSN

1520-6106

e-ISSN

1520-5207

Svazek periodika

127

Číslo periodika v rámci svazku

27

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

6078-6090

Kód UT WoS článku

001015992700001

EID výsledku v databázi Scopus

2-s2.0-85164374349