Influence of Potassium Ions on Act of Amphotericin B to the DPPC/Chol Mixed Monolayer at Different Surface Pressures

Abstract

Amphotericin B (AmB) is an antifungal drug that rarely develops resistance. It has an affinity with the cholesterol on mammalian cell membranes, disrupting the structure and function of the membranes, which are also affected by potassium ions. However, the mechanism is unclear. In this paper, the Langmuir monolayer method was used to study the effects of potassium ions on the surface pressure–mean molecular area of isotherms, elastic modulus and the surface pressure–time curves of a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol (DPPC/Chol) monolayer and a DPPC/Chol/AmB monolayer. The morphology and thickness of the Langmuir–Blodgett films were studied via atomic force microscopy. The results showed that AmB can increase the mean molecular area of the DPPC/Chol mixed monolayer at low pressures (15 mN/m) but reduces it at high pressures (30 mN/m). The potassium ions may interfere with the effect of AmB in different ways. The potassium ions can enhance the influence of AmB on the stability of monolayer at low surface pressures, but weaken it at high surface pressures. The potassium ions showed significant interference with the interaction between AmB and the cholesterol-enriched region. The results are helpful for us to understand how the effect of amphotericin B on the phospholipid membrane is interfered with by potassium ions when amphotericin B enters mammalian cell membrane.