The ligand-gated ion channel resides partly in the cell membrane, which is its working environment. Currently, I am investigating how small molecules interact with membranes, and affect the functions of the membrane proteins.
The cell membrane has long been thought to be involved in general anaesthetic action, but it has never been clear how. The effect of general anaesthetics is pressure-dependent; increased ambient pressure reverses their effects. Electron-spin spectroscopy experiments showed that halothane altered the order parameter of a phosphatidylcholine membrane, but this change was reversed when the pressure of the system was raised to 274 atm. However, the molecular mechanism of this pressure-induced reversal was unclear. Using simulations, we have shown that at 200 atm - 400 atm, halothane tends to aggregate inside the membrane.
The diagram on the right shows the relative probability of halothane being found in the xy-plane of the membrane. The top panel shows the probability at 105 Pa (1 atm), the middle panel at 2×107 Pa (200 atm), and the bottom panel at 4×107 Pa (400 atm). The redder the colour, the higher the relative probability of finding a halothane molecule in that location. Aggregation at high pressures is obvious.
I am currently planning neutron scattering and Brewster angle microscopy experiments with Steve Roser (Department of Chemistry, University of Bath) to verify these findings. I am also collaborating with Matubayasi Nobuyuki (Institute for Chemical Research, Kyoto University) to evaluate the free energy change of halothane aggregation at different pressures.![[hydrated DMPC with halothane]](contour.png)