Magnetically aligned bicelles to study the orientation of lipophilic ligands in membrane bilayers

Magnetically aligned bicelles were used as a model membrane to study the orientation and dynamic properties of two cannabinoids (Delta (8)-THC and Me-Delta (8)-THC) using (31)P and (2)H NMR. The uniform alignment of the bicelles allowed us to obtain well resolved deuterium spectra from a solution NMR spectrometer. The preferred orientations of Delta (8)-THC and Me-Delta (8)-THC were calculated on the basis of the measurements of individual quadrupolar splittings. Our results agree with previous experiments using multilamellar membranes as well as with molecular dynamics simulation data described here. In conjunction with our earlier report using small and fast tumbling bicelles, the present work of well aligned bicelles shows that bicelle preparations can provide either pseudoisotropic or anisotropic NMR spectra to study the conformation, orientation, and dynamic properties of ligands in membrane bilayers. Such data are of critical value for understanding the interactions of lipophilic drug molecules with membrane proteins.