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Biophys. J. BioFAST: First Published December 21, 2004. doi:10.1529/biophysj.104.044354
© 2004 by the Biophysical Society.

A more recent version of this article appeared on March 1, 2005.
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BIOPHYSICAL THEORY AND MODELING

CONCENTRATION EFFECTS OF VOLATILE ANESTHETICS ON THE PROPERTIES OF MODEL MEMBRANE: A COARSE GRAIN APPROACH

Monica Pickholz 1*, Leonor Saiz 2 and Michael L. Klein 3

1 UNICAMP
2 CMM,University of Pennsylvania
3 LRSM, University of Pennsylvania

* To whom correspondence should be addressed. E-mail: monik{at}ifi.unicamp.br.

Submitted on April 17, 2004
Revised on May 30, 2004
Accepted on 5 November 2004


  Abstract
In order to gain insights into the molecular level mechanism of drug action at the membrane site,we have carried out extensive molecular dynamics (MD) simulations of a model membrane in the presence of a volatile anesthetic (VA) using a coarse grain (CG) model. Six different anesthetic(halothane):lipid (dimyristoylphosphatidylcholine, DMPC)ratios have been investigated, going beyond the low doses typical of medical applications. The VA were introduced into a preassembled fully hydrated 512-molecule lipid bilayer and each of the MD simulations were carried out at ambient conditions, using the NPT ensemble.The area per lipid increases monotonically with the halothane concentration and the lamellar spacing decreases, whereas the lipid bilayer thickness shows no appreciable differences and only a slight increase upon addition of halothane. The density profiles of the anesthetic molecules display a bimodal distribution along the membrane normal with maxima located close to the lipid-water interface region.We have studied how halothane molecules {\it fluctuate} between the two maxima of the bimodal distribution and we observed a different mechanism at low and high anesthetic concentrations. Through the investigation of the reorientational motions of the lipid tails, we found that the anesthetic molecules increase the segmental order of the lipids close to the membrane surface.

Key Words: coarse grain, model membrane, molecular dynamics, volatile anesthetic




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Copyright © 2004 by the Biophysical Society.