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Updated: Jul 9, 2026

Neutron Spin Echo Spectroscopy as a Unique Probe for Lipid Membrane Dynamics and Membrane-Protein Interactions
Published on: May 27, 2021
The dynamics and orientation of a lipophilic drug within model membranes determined by 13C solid-state NMR
Martin P Boland1, David A Middleton
1Faculty of Life Sciences, University of Manchester, P.O. Box 88, Sackville Street, Manchester, UK M60 1DQ.
Abstract:
Methods for determining how a drug interacts with cellular membranes at the molecular level can give valuable insight into the mode of action of the drug and its absorption, distribution and metabolism profile. A procedure is described here to determine the orientation and location of the lipophilic drug trifluoperazine (TFP) intercalated into dimyristoylphosphatidylcholine (DMPC) bilayers, by using a novel combination of high-resolution solid-state nuclear magnetic resonance (SSNMR) methods to observe signals from (13)C within the drug at natural abundance. SSNMR measurements of (1)H-(13)C dipolar couplings for TFP and selective broadening of (13)C NMR peaks by paramagnetic Mn(2+) together suggest a model for the location, orientation and dynamics of the drug within lipid bilayers that offers an explanation for the lysoprotective effect of the drug at low concentrations. The experiments described are straightforward to implement and can be used for the routine analysis of drug-membrane interactions to provide useful information for drug design and structure refinement.
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