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Biophysical Journal 84:3123-3137 (2003)
© 2003 The Biophysical Society

Interaction between Artificial Membranes and Enflurane, a General Volatile Anesthetic: DPPC-Enflurane Interaction

Nathalie Hauet *, Franck Artzner *, François Boucher {dagger}, Cécile Grabielle-Madelmont *, Isabelle Cloutier {dagger}, Gérard Keller *, Pierre Lesieur {ddagger}, Dominique Durand {ddagger} and Maïté Paternostre *

* Equipe "Physicochimie des Systèmes Polyphasés," UMR 8612, Université Paris Sud, F-92296 Châtenay Malabry, France; {dagger} Département de Chimie Biologie et Groupe de Recherche sur l'Énergie et l'Information Biomoléculaires, Université du Québec à Trois Rivières, Trois Rivières, Québec, Canada G9A-5H7; and {ddagger} Laboratoire pour l'Utilisation du Rayonnement Electromagnétique, Université Paris Sud, F-91405 Orsay, France

Correspondence: Address reprint requests to Maïté Paternostre, URA 2096 CNRS-CEA, DBJC/SBFM Bat. 528, CEA-Saclay, 91190 Gif/Yvette, France. Tel.: 33-016-908-6749; E-mail: maite.paternostre{at}cea.fr.

The structural modifications of the dipalmitoylphosphatidylcholine (DPPC) organization induced by increasing concentration of the volatile anesthetic enflurane have been studied by differential scanning calorimetry, small-angle, and wide-angle x-ray scattering. The interaction of enflurane with DPPC depends on at least two factors: the enflurane-to-lipid concentration ratio and the initial organization of the lipids. At 25°C (gel state), the penetration of enflurane within the lipids induces the apparition of two different mixed lipid phases. At low anesthetic-to-lipid molar ratio, the smectic distance increases whereas the direction of the chain tilt changes from a tilt toward next-neighbors to a tilt between next-neighbors creating a new gel phase called Lß'2NNN. At high ratio, the smectic distance is much smaller than for the pure Lß' DPPC phase, i.e., 50 Å compared to 65 Å, the aliphatic chains are perpendicular to the membrane and the fusion temperature of the phase is 33°C. The electron profile of this phase that has been called Lßi, indicates that the lipids are fully interdigitated. At 45°C (fluid state), a new melted phase, called L{alpha}2, was found, in which the smectic distance decreased compared to the initial pure L{alpha}1 DPPC phase. The thermotropic behavior of the mixed phases has also been characterized by simultaneous x-ray scattering and differential scanning calorimetry measurements using the Microcalix calorimeter of our own. Finally, titration curves of enflurane effect in the mixed lipidic phase has been obtained by using the fluorescent lipid probe Laurdan. Measurements as a function of temperature or at constant temperature, i.e., 25°C and 45°C give, for the maximal effect, an enflurane-to-lipid ratio (M/M), within the membrane, of 1 and 2 for the L{alpha}2 and the Lßi lamellar phase respectively. All the results taken together allowed to draw a pseudo-binary phase diagram of enflurane-dipalmitoylphosphatidylcholine in excess water.




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