113Cd-, 31P-NMR and fluorescence polarization studies of cadmium(II) interactions with phospholipids in model...

Cadmium(II) interactions with multilamellar vesicles of dimyristoyl (DM)- and dipalmitoyl (DP)-phosphatidylcholine (PC), -phosphatidylserine (PS), -phosphatidic acid (PA), -phosphatidylglycerol (PG) and -phosphatidylethanolamine (PE) have been investigated both from the metal and the membrane viewpoints, respectively, by solution 113Cd-NMR and diphenylhexatriene fluorescence polarization coupled with solid-state 31P-NMR. Results can be summarized as follows. (1) Strong cadmium binding to membrane phospholipids results in a decrease of the free Cd(II) 113Cd-NMR isotropic signal and because of slow exchange, in the NMR time scale, between free and bound cadmium pools, the lipid/water partition coefficients, Klw, of the Cd(II) species can be determined in the lamellar gel (fluid) phase. It is found Klw(DMPC) approximately Klw(EggPE) approximately 2+/-2 (2+/-2); Klw(DMPA)=392+/-20 (505+/-25); Klw(DMPG)=428+/-21 (352+/-17); Klw(DMPS)=544+/-27 (672+/-34). Cadmium interactions with membrane phospholipids are therefore electrostatic in nature and the phosphate moiety is proposed as a potential binding site. (2) The presence of Cd(II) stabilizes the gel phases of PG, PA and PS lipids and leads to suppression of the main phase transition for PA and PS. These effects are reduced upon increasing salinity to 0.5 M Cl- and abolished at 1.8 M Cl-, Cd(II) being removed from the membranes due to formation of soluble CdCln species. Moving the pH from 7 to 6 also decreases Cd(II) binding to PA, because of surface charge reduction. (3) Cadmium promotes the formation of isotropic 31P-NMR lines with PG systems and of a hexagonal phase on egg PE bilayers at 24 degreesC, suggesting dramatic membrane reorganization. Properties of cadmium and calcium interacting with phospholipid model membranes are compared, and the potential roles of these interactions in the molecular mechanisms of cadmium uptake and toxicity in cells are discussed.