CD-113-NMR, P-31-NMR AND FLUORESCENCE POLARIZATION STUDIES OF CADMIUM(II) INTERACTIONS WITH PHOSPHOLIPIDS IN MODEL MEMBRANES

Cadmium(II) interactions with multilamellar vesicles of dimyristoyl (D M)- and dipalmitoyl (DP)-phosphatidylcholine (PC), -phosphatidylserine (PS), -phosphatidic acid (PA), -phosphatidylglycerol (PG) and -phosph atidylethanolamine (PE) have been investigated both from the metal and the membrane viewpoints, respectively, by solution Cd-113-NMR and dip henylhexatriene fluorescence polarization coupled with solid-state P-3 1-NMR. Results can be summarized as follows. (1) Strong cadmium bindin g to membrane phospholipids results in a decrease of the free Cd(II) C d-113-NMR isotropic signal and because of slow exchange, in the NMR ti me scale, between free and bound cadmium pools, the lipid/water partit ion coefficients, K-lw, of the Cd(II) species can be determined in the lamellar gel (fluid) phase. It is found K-lw (DMPC)approximate to K-l w(EggPE)approximate to 2 +/- 2 (2 +/- 2); K-lw(DMPA)= 392 +/- 20 (505 +/- 25); K-lw(DMPG) = 428 +/- 21. (352 +/- 17); K-lw(DMPS)= 544 +/- 27 (672 +/- 34), Cadmium interactions with membrane phospholipids are th erefore electrostatic in nature and the phosphate moiety is proposed a s 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 mai n phase transition for PA and PS. These effects are reduced upon incre asing salinity to 0.5 M Cl- and abolished at 1.8 M Cl-, Cd(II) being r emoved from the membranes due to formation of soluble CdCln species. M oving the pH from 7 to 6 also decreases Cd(II) binding to PA, because of surface charge reduction. (3) Cadmium promotes the formation of iso tropic P-31-NMR lines with PG systems and of a hexagonal phase on egg PE bilayers at 24 degrees C, suggesting dramatic membrane reorganizati on. Properties of cadmium and calcium interacting with phospholipid mo del membranes are compared, and the potential roles of these interacti ons in the molecular mechanisms of cadmium uptake and toxicity in cell s are discussed. (C) 1998 Elsevier Science B.V, All rights reserved.