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

Author(s)
Balazs Fabian, Marcello Sega, Vladimir P. Voloshin, Nikolai N. Medvedev, Pal Jedlovszky
Abstract

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(s)
Computational and Soft Matter Physics
External organisation(s)
Budapest University of Technology and Economics, University of Burgundy, 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
Volume
121
Pages
2814-2824
No. of pages
11
ISSN
1520-6106
DOI
https://doi.org/10.1021/acs.jpcb.7b00990
Publication date
04-2017
Peer reviewed
Yes
Austrian Fields of Science 2012
103015 Condensed matter, 104022 Theoretical chemistry
Keywords
ASJC Scopus subject areas
Materials Chemistry, Surfaces, Coatings and Films, Physical and Theoretical Chemistry
Portal url
https://ucrisportal.univie.ac.at/en/publications/985ea737-5b0a-4ad2-8467-42af2436aec0