Hg2+ and Cd2+ interact differently with biomimetic erythrocyte membranes

Abstract

In order to characterize the potentially deleterious effects of toxic Hg(2+) and Cd(2+) on lipid membranes, we have studied their binding to liposomes whose composition mimicked erythrocyte membranes. Fluorescence spectroscopy utilizing the concentration dependent quenching of Phen Green SK by Hg(2+) and Cd(2+) was found to be a sensitive tool to probe these interactions at metal concentrations < or =1 microM. We have systematically developed a metal binding affinity assay to screen for the interactions of Hg(2+) or Cd(2+) with certain lipid classes. A biomimetic liposome system was developed that contained four major lipid classes of erythrocyte membranes (zwitterionic lipids: phosphatidylcholine and phosphatidylethanolamine; negatively charged: phosphatidylserine and neutral: cholesterol). In contrast to Hg(2+), which preferentially bound to the negatively charged phosphatidylserine compared to the zwitterionic components, Cd(2+) bound stronger to the two zwitterionic lipids. Thus, the observed distinct differences in the binding affinity of Hg(2+) and Cd(2+) for certain lipid classes together with their known effects on membrane properties represent an important first step toward a better understanding the role of these interactions in the chronic toxicity of these metals.

Mercury-sensitive water channels as possible sensors of water potentials in pollen

“…Many of its recognized toxic effects are related to its entry into the circulation in the animal body, and this aspect will not be considered here. Hg 2+ , when applied at high concentration, can interact with lipid bilayers by changing membrane fluidity and binding to certain lipid sites ( Delnomdedieu and Allis, 1993 ; Suwalsky et al , 2000 ; Garcia et al , 2005 ; Le et al , 2009 ). Lipid bilayers are permeable to HgCl 2 as a neutral molecule ( Gutknecht, 1981 ) but, where Hg 2+ ions are concerned, rapid effects are confined to its action on membrane proteins; external application of HgCl 2 only results in binding when thiol groups in hydrophilic clefts have surface access to the medium ( Kiss and Osipenko, 1994 ; Krajewska, 2008 ).…”

Cell organelles as targets of mammalian cadmium toxicity

“…Whereas cadmium uptake and cadmium transport mechanisms into the intracellular space have been well characterized, less is known about the impact of cadmium on lipid bilayers. Using liposomes to mimic the outer leaflet of the erythrocyte PM, cadmium interacts preferentially with phosphatidylethanolamine, but not with cholesterol (Le et al 2009), causing tighter lipid packing through dissipation of opposing negative charges and thus increasing membrane rigidity though without changes in lateral organization (reviewed in Payliss et al (2015)). Increased PM rigidity by cadmium could be confirmed in PMs isolated from human kidney proximal tubule cells (PTCs) exposed to 5 µM cadmium for 6 h (Sule, K., Prenner, E.J., Lee, W.K., unpublished data).…”

Metal Species in Biology: Bottom-Up and Top-Down LC Approaches in Applied Toxicological Research

“…In the bloodstream the ligand(s) which a particular metal species will bind to is determined by (a) its affinity for each available binding site (e.g., on plasma proteins, external membrane receptors, and/or on cell membranes [85]) and (b) the relative concentration of all binding sites [86]. This binding event often involves the coordination of the metal species to nitrogen, oxygen, and sulfur donor atoms on peptides and proteins [87].…”