A study of the effect of anaesthetic molecules on model membranes formed in surfactant / water mixtures

Abstract

This work studies the effect of a range of general and local anaesthetics on model membranes, aiming to establish if the addition of anaesthetic promotes changes in the membranes interfacial region or within their internal structure. The models used for biological membranes were simple surfactantiwater systems, which have been previously well studied and characterised. The phases they form are sensitive to changes in composition and interfacial architecture, though they lack the complexity of real membranes.
Previous studies on anaesthetics suggest that their effect on membranes was to make them leaky. Therefore, the starting point of this project was to propose that pore formation might be a possible explanation for the anaesthetic action upon model membranes. The study focused on three model membrane systems and used techniques such as NMR and SAXS to obtain information about any structural changes that may occur as a result of anaesthetic addition.
The work started with concentrated surfactant water systems that exhibit bilayer like structures (i.e. larnellar phase L. and porous lamellar phase). Two surfactantlwater systems, the ionic surfactant AOT/ 2H20 and the non-ionic surfactant C16EO/ 2H20, were chosen.
AOT/2H20 displays a large lamellar phase region stable over a wide range of temperatures and concentration. It was studied to see if the anaesthetic addition triggers the formation of another phase. It was found that anaesthetics induce dehydration, but no dramatic changes in the phase stability were identified for phases which are not close to a transition boundary. In the C16E06/ 2H20 system there are a porous laniellar phase and a classical lamellar phase, which allowed the effect of anaesthetic on the stability of the existing pores to be studied. In this case the anaesthetics fall into two types with respect to their effect: type I that reduces the curvature in the system and another type II that seems to favour higher curvature in
the system at higher temperatures with respect to the binary system.
The generality of this observation was then tested upon more biologically realistic systems in terms of surfactant to water ratio. In the non-ionic C 10E03/21-120 system, the effect of anaesthetic was studied on the lamellar phase (La) to the sponge phase (L3) topological phase transition in both unbuffered and buffered solutions (pH = 7.4). In the unbuffered system the results mirrored the behaviour in the concentrated systems, whilst in the buffered system both types of anaesthetic tend to dehydrate the surface and suppress interfacial curvature. It seems that, under physiological conditions (pH = 7.4), all anaesthetics have a tendency to reduce interfacial curvature. This contradicts the original hypothesis that anaesthetics may promote pore formation, i.e. "leaky" membranes.