Whilst fungal membranes contain called ergosterol, animal cell membranes, including our own, contain the more familiar cholesterol. It is thought that AmB reacts more readily with ergosterol to form these membrane holes than it does with cholesterol. This would explain why at low doses AmB can be used to treat infection without harming the patient, however there has so far been no direct evidence to support this hypothesis.
Structural analysis by neutron diffraction at the ILL
In this new paper, Dr David Barlow and his colleagues from King's College London describe neutron diffraction experiments at the Institut Laue-Langevin, the flag-ship centre for neutron science that reveal how AmB interacts with fungal and animal cell membranes on sub-molecular scales of around 1 millionth the width of a human hair.
Like all particles, neutrons demonstrate some wave like behaviour, and when they encounter obstacles whose size is comparable with their wavelength they scatter along well-defined angles. It is this property which allows scientists at neutron sources such as the ILL to analyse the scattering patterns and infer the structure of the material the neutrons have passed through.
The team modelled the two different membranes with layers of lipids, fatty molecules found in all cells, which were combined with either cholesterol or ergosterol. The team used deuteration techniques where deuterium, a heavier isotope of hydrogen which is easily picked out by neutrons over its lighter cousin, is introduced to either the membrane model or the drug, tagging that part of the system to follow it during the interaction.
Using these techniques the team unveiled the first experimental evidence for the theoretical 'leaky holes' resulting from the development of 'barrel-like' structures which formed in both membranes upon the introduction of AmB.
However, the barrels were fo
|Contact: James Romero|
King's College London