Influence of amphotericin B on liquid crystal state of the Cholesterol/Dipalmitoylphosphatidylcholine monolayer in the presence of different metal cations*

Amphotericin B is a very effective antifungal drug, but it has an adverse reaction to the membrane of mammals' cells. The interaction between AmB and cholesterol (Chol) causes the formation of pores on the membrane to destroy its integrity. In particular, AmB has a significant effect on the permeability of membrane for K+ ions. It has been reported that Na+ ions and Ca2+ ions may have some influence on the interaction between amphotericin B and lipid molecules. In this work, the effects of these metal cations on the physical state and intermolecular interaction of the Cholesterol/ Dipalmitoylphosphatidylcholine (Chol/DPPC) monolayer with and without AmB have been investigated. The addition of AmB induces the change of physical state of the lipid monolayer from liquid-gel phase to liquid phase. Different metal cations could influence the phase transition of the AmB-lipid monolayer. The K+ ions and Ca2+ ions make the obvious phase transition disappear. However, the presence of Na+ ions has little influence on the phase transition of the AmB-lipid monolayer. The addition of AmB and the presence of different metal cations weaken the attractive force on the monolayers. After addition of AmB, the force between the molecules is the strongest in the environment of K+ ions, thus is the weakest in the environment of Ca2+ ions, which may be due to the distribution of these metal cations inside and outside of cells. A large number of K+ ions distribute inside of the cells, thus most of Na+ and Ca2+ ions exist out of the cells. Hence, it may be possible that when AmB molecules are out of the cells, the reaction between the drug and lipid molecules is weaker than that inside the cells. These results may have a great reference value for further studying the toxicity mechanism of AmB and the influence of metal cations on the membrane.