THE EFFECT OF ANESTHETICS ON THE DYNAMIC HETEROGENEITY OF LIPID-MEMBRANES

The influence of membrane-perturbing drugs such as anaesthetics on the lipid membrane properties is analyzed theoretically on the basis of a general microscopic interaction model of the gel-to-fluid chain melti ng transition of one-component phospholipid membranes and phospholipid membranes with a low content of cholesterol. Monte Carlo computer sim ulation of the model shows that the gel-to-fluid transition of the lip id membrane, manifested in the formation of dynamically coexisting dom ains of gel and fluid lipids, is strongly influenced by the presence o f anaesthetics. Macroscopically the effect of anaesthetics on the memb rane properties is seen in a depression of the transition temperature and a smearing of thermodynamic response functions like the specific h eat. Microscopically the calculations reveal that anaesthetics have a high affinity to the fluctuating domain interfaces that are dominated by kink-like lipid-chain conformations. This leads to formation of mor e interfaces and to a locally high concentration of anaesthetics in th e interfacial regions, which is much larger than the global concentrat ion in the membrane. Important membrane components like cholesterol, w hich also has been shown to be interfacially active, are found to decr ease the absorption of anaesthetics and to squeeze out anaesthetics fr om the interfaces. The results of the general model study of anaesthet ics-membrane interactions are discussed in relation to both general an aesthetics, like halothane, and local anaesthetics like cocaine-deriva tives.