Lateral Pressure Profile and Free Volume Properties in Phospholipid Membranes Containing Anesthetics

Autor(en)

Balazs Fabian, Marcello Sega, Vladimir P. Voloshin, Nikolai N. Medvedev, Pal Jedlovszky

Abstrakt

The effect of four general anesthetics, namely chloroform, halothane, diethyl ether, and enflurane on the free volume fraction and lateral pressure profiles in a fully hydrated dipalmitoylphosphatidylcholime (DPPC) membrane is investigated by means of computer simulation. In order to find changes that can be related to the molecular mechanism of anesthesia as well as its pressure reversal, the simulations are performed both at atmospheric and high (1000 bar) pressures. The obtained results show that the additional free volume occurring in the membrane is localized around the anesthetic molecules themselves. Correspondingly, the fraction of the free volume is increased in the outer of the two membrane regions (i.e., at the outer edge of the hydrocarbon phase) where anesthetic molecules prefer to stay in every case. As a consequence, the presence of anesthetics decreases the lateral pressure in the nearby region of the lipid chain ester groups, in which the anesthetic molecules themselves do not penetrate. Both of these changes, occurring upon introducing anesthetics in the membrane, are clearly reverted by the increase of the global pressure. These findings are in accordance both with the more than 60 years old "critical volume hypothesis" of Mullins, and with the more recent "lateral pressure hypothesis" of Cantor. Our results suggest that if anesthesia is indeed caused by conformational changes of certain membrane-bound proteins, induced by changes in the lateral pressure profile, as proposed by Cantor, the relevant conformational changes are expected to occur in the membrane region where the ester groups are located.

Organisation(en)

Computergestützte Physik und Physik der Weichen Materie

Externe Organisation(en)

Budapest University of Technology and Economics, Université de Bourgogne, Russian Academy of Sciences, Novosibirsk State University (NSU), Eszterházy Károly University of Applied Sciences, Eötvös Loránd University Budapest

Journal

The Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical

Band

121

Seiten

2814-2824

Anzahl der Seiten

11

ISSN

1520-6106

DOI

https://doi.org/10.1021/acs.jpcb.7b00990

Publikationsdatum

04-2017

Peer-reviewed

Ja

ÖFOS 2012

103015 Kondensierte Materie, 104022 Theoretische Chemie

Schlagwörter

ASJC Scopus Sachgebiete

Materials Chemistry, Surfaces, Coatings and Films, Physical and Theoretical Chemistry

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/985ea737-5b0a-4ad2-8467-42af2436aec0