Effect of incorporation of drugs, vitamins and peptides on the structure and dynamics of lipid assemblies.
The characteristics of vesicles formed from Dipalmitoyl Phosphatidyl Choline (DPPC) are sensitive to the presence of perturbing molecules such as drugs, peptides, hormones and vitamins. We have used ESR spin labeling and NMR techniques for studying interaction of such molecules with lipid bilayers. ESR spin labeling has been used to monitor thermotropic behaviour of model membranes. Different NMR probes such as 1H, 31P, 13C have been used to gather information regarding the mode of interaction. It has been observed that the model membrane systems respond differently depending upon the localization of the perturbing molecules in the lipid bilayer. Small molecules such as neurotransmitters epinephrine and norepinephrine decrease gel to liquid crystalline phase transition temperature significantly even when present in small amounts. Vitamin E acetate having a hydrophobic hydrocarbon tail orients parallel to the lipid molecule and thereby exhibits dynamics similar to palmitate chain. When the acetate group is replaced by hydroxyl group (alpha-tocopherol), the phase transition becomes broad and the lipid molecules loose freedom of lateral diffusion. This can be attributed to formation of hydrogen bond between the hydroxyl group of alpha-tocopherol and phosphate moiety of lipid. The conformation of antidepressants nitroxazepine and imipramine is significantly altered when embedded in lipid bilayer. Anaesthetic etomidate not only modifies thermotropic characteristics but also induces polymorphism. The normal bilayer arrangement of lipids gets transformed into hexagonal packing. Amino acid tryptophan induces cubic phases in the normal bilayer arrangement of DPPC dispersions. Peptide gonadoliberin shows a reduced internal motion due to the lipid peptide interaction. The major consequences of binding of lipids with externally added molecules are changes in the fluidity and permeability properties of membranes. It has been shown that permeability is effected by the presence of molecules such as propranolol, alpha-tocopherol and its analogue, neurotransmitters, etc. The magnetic resonance methods have thus evolved as power techniques in the study of membrane structure and function.
Srivastava
S
S
Tata Institute of Fundamental Research, Bombay, India.
Phadke
R S
RS
Govil
G
G
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D008051:Lipid Bilayers; D050356:Lipid Metabolism; D010455:Peptides / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014815:Vitamins / Q000494:pharmacology
D008051:Lipid Bilayers; D010455:Peptides; D014815:Vitamins; D015060:1,2-Dipalmitoylphosphatidylcholine; D011433:Propranolol