Interaction of amphotericin B with lipid monolayers

Area of Science:

• Biophysics
• Membrane Biophysics
• Drug-Membrane Interactions

Background:

• Amphotericin B (AmB) is a crucial antifungal agent.
• Understanding AmB's interaction with cell membranes is key to its selective toxicity.
• Mimicking cell membranes with lipid monolayers allows for controlled study of drug interactions.

Purpose of the Study:

• To investigate the interaction of Amphotericin B (AmB) with model cell membranes.
• To compare AmB's behavior with lipid monolayers mimicking fungal (POPC/ergosterol) and mammalian (POPC/cholesterol) membranes.
• To elucidate the biophysical mechanisms underlying AmB's selective antifungal activity.

Main Methods:

• Langmuir isotherm analysis to measure surface pressure changes.
• Neutron reflectivity to probe monolayer structural alterations.
• Brewster angle microscopy to visualize domain formation and dynamics.

Main Results:

• AmB induced more rapid and pronounced changes in surface pressure and domain formation in fungal-mimicking POPC/ergosterol monolayers compared to mammalian-mimicking POPC/cholesterol and POPC monolayers.
• Neutron reflectivity confirmed similar AmB insertion into all monolayer types, with its macrocyclic ring intercalating lipids and sterols.
• Distinct in-plane structures and differing kinetics of interaction were observed across the model membrane systems.

Conclusions:

• Amphotericin B inserts into lipid monolayers with similar structural orientation but exhibits differential kinetics and in-plane organization.
• The observed differences in interaction dynamics and domain formation correlate with AmB's known selectivity for fungal over mammalian cell membranes.
• These findings provide biophysical insights into the molecular basis of Amphotericin B's antifungal efficacy and target specificity.