K. Jorgensen et al., THE EFFECT OF ANESTHETICS ON THE DYNAMIC HETEROGENEITY OF LIPID-MEMBRANES, Chemistry and physics of lipids, 65(3), 1993, pp. 205-216
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.