Membrane structural perturbations caused by anesthetics and nonimmobilizers: a molecular dynamics investigation.
The structural perturbations of the fully hydrated dimyristoyl-phosphatidylcholine bilayer induced by the presence of hexafluoroethane C(2F6), a "nonimmobilizer," have been examined by molecular dynamics simulations and compared with the effects produced by halothane CF3CHBrCl, an "anesthetic," on a similar bilayer (DPPC) (Koubi et al., Biophys. J. 2000. 78:800). We find that the overall structure of the lipid bilayer and the zwitterionic head-group dipole orientation undergo only a slight modification compared with the pure lipid bilayer, with virtually no change in the potential across the interface. This is in contrast to the anesthetic case in which the presence of the molecule led to a large perturbation of the electrostatic potential across to the membrane interface. Similarly, the analysis of the structural and dynamical properties of the lipid core are unchanged in the presence of the nonimmobilizer although there is a substantial increase in the microscopic viscosity for the system containing the anesthetic. These contrasting perturbations of the lipid membrane caused by those quite similarly sized molecules may explain the difference in their physiological effects as anesthetics and nonimmobilizers, respectively.
Koubi
L
L
Center for Molecular Modeling, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, USA.
Tarek
M
M
Bandyopadhyay
S
S
Klein
M L
ML
Scharf
D
D
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000777:Anesthetics / Q000494:pharmacology*; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D007202:Indicators and Reagents / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry; D008567:Membranes, Artificial; D008962:Models, Theoretical; D012984:Software; D055672:Static Electricity; D013997:Time Factors
D000777:Anesthetics; D007202:Indicators and Reagents; D008051:Lipid Bilayers; D008055:Lipids; D008567:Membranes, Artificial; D015060:1,2-Dipalmitoylphosphatidylcholine; D004134:Dimyristoylphosphatidylcholine