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Updated: May 17, 2026
Neutron Spin Echo Spectroscopy as a Unique Probe for Lipid Membrane Dynamics and Membrane-Protein Interactions
Published on: May 27, 2021
Neutron diffraction studies of the interaction between amphotericin B and lipid-sterol model membranes
Fabrizia Foglia1, M Jayne Lawrence, Bruno Demeė
1Institute of Pharmaceutical Science, King's College London, London, UK.
Abstract:
Over the last 50 years or so, amphotericin has been widely employed in treating life-threatening systemic fungal infections. Its usefulness in the clinic, however, has always been circumscribed by its dose-limiting side-effects, and it is also now compromised by an increasing incidence of pathogen resistance. Combating these problems through development of new anti-fungal agents requires detailed knowledge of the drug's molecular mechanism, but unfortunately this is far from clear. Neutron diffraction studies of the drug's incorporation within lipid-sterol membranes have here been performed to shed light on this problem. The drug is shown to disturb the structures of both fungal and mammalian membranes, and co-localises with the membrane sterols in a manner consistent with trans-membrane pore formation. The differences seen in the membrane lipid ordering and in the distributions of the drug-ergosterol and drug-cholesterol complexes within the membranes are consistent with the drug's selectivity for fungal vs. human cells.
Insights
Amphotericin treats fungal infections but causes side effects and resistance. Neutron diffraction reveals it forms pores in fungal and mammalian membranes, explaining its selective toxicity.
Area of Science:
- Biophysics
- Structural Biology
- Antimicrobial Research
Background:
- Amphotericin is a vital antifungal drug for systemic infections.
- Clinical use is limited by severe side effects and emerging drug resistance.
- Understanding amphotericin's molecular mechanism is crucial for developing new antifungals.
Purpose of the Study:
- To elucidate the molecular mechanism of amphotericin action.
- To investigate amphotericin's interaction with lipid-sterol membranes using neutron diffraction.
Main Methods:
- Neutron diffraction studies were conducted.
- The incorporation and effects of amphotericin within fungal and mammalian membranes were analyzed.
- Interactions with membrane sterols (ergosterol and cholesterol) were examined.
Main Results:
- Amphotericin disrupts the structure of both fungal and mammalian membranes.
- The drug co-localizes with membrane sterols, suggesting trans-membrane pore formation.
- Differences in membrane lipid ordering and drug-sterol complex distribution indicate selective toxicity towards fungal cells.
Conclusions:
- Neutron diffraction provides insights into amphotericin's membrane interaction and pore-forming capability.
- Observed differences in drug-sterol interactions explain amphotericin's selective toxicity against fungal pathogens.
- This research aids in the rational design of novel antifungal agents with improved profiles.
