NMR investigations of interactions between anesthetics and lipid bilayers.
Interactions between anesthetics (lidocaine and short chain alcohols) and lipid membranes formed by dimyristoylphosphatidylcholine (DMPC) were studied using NMR spectroscopy. The orientational order of lidocaine was investigated using deuterium NMR on a selectively labelled compound whereas segmental ordering in the lipids was probed by two-dimensional 1H-13C separated local field experiments under magic-angle spinning conditions. In addition, trajectories generated in molecular dynamics (MD) computer simulations were used for interpretation of the experimental results. Separate simulations were carried out with charged and uncharged lidocaine molecules. Reasonable agreement between experimental dipolar interactions and the calculated counterparts was observed. Our results clearly show that charged lidocaine affects significantly the lipid headgroup. In particular the ordering of the lipids is increased accompanied by drastic changes in the orientation of the P-N vector in the choline group.
Castro
Vasco
V
Division of Physical Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden.
Stevensson
Baltzar
B
Dvinskikh
Sergey V
SV
Högberg
Carl-Johan
CJ
Lyubartsev
Alexander P
AP
Zimmermann
Herbert
H
Sandström
Dick
D
Maliniak
Arnold
A
D000777:Anesthetics / Q000737:chemistry / Q000378:metabolism*; D003903:Deuterium; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry / Q000378:metabolism; D008012:Lidocaine / Q000737:chemistry / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy
D000777:Anesthetics; D008051:Lipid Bilayers; D008012:Lidocaine; D003903:Deuterium; D004134:Dimyristoylphosphatidylcholine