Differential impact of single and binary metal mixtures on membrane biophysics as determined by fluorescence and nuclear magnetic resonance spectroscopy
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Heavy metals are toxic to bacterial and eukaryotic organisms. In humans, they are associated with Alzheimer's disease and various cancers. Metals like gadolinium, cadmium, lead, and mercury can bioaccumulate. Lipids are a known metal target in biomembranes. Although metal-lipid interactions have been studied, interactions of metal mixtures are not well understood. This study of binary mixtures of Gd, Cd, and Pb addresses their impact on membrane fluidity and phase transition from rigid gel to fluid liquid-crystalline phases by using fluorescence spectroscopy, in particular Laurdan generalized polarization (GP). Laurdan GP results showed that Gd with its 3+ charge outcompeted the effects of Cd and Pb and induced the largest rigidification. Binary mixtures of Hg/Cd or Pb/Cd showed a higher affinity of Hg and Pb for chloride than Cd. It is known that under physiological conditions some inorganic metals form chloro-complexes. Speciation was considered by using 113Cd, 199Hg, nuclear magnetic resonance. Mixtures of Pb, Cd, and Hg were examined to determine whether their speciation were similar to calculated speciation. Lastly, the Hg induced cleavage of a specific lipid class, plasmalogens was known without a detailed understanding of the mechanism. 1H and 13C nuclear magnetic resonance were used but more work is needed to determine the final step of the mechanism. These studies investigated potential contributions of metal toxicity at the membrane level for bioaccumulating metals of concern, but also included the impact of metal mixtures, which has not been sufficiently investigated in the field.