Effects of Al3+ and Related Metals on Membrane Phase State and Hydration: Correlation with Lipid Oxidation

The aim of the present study was to further understand how changes in membrane organization can lead to higher rates of lipid oxidation. We previously demonstrated that Al3+, Sc3+, Ga3+, Be2+, Y3+, and La3+ promote lipid packing and lateral phase separation. Using the probe Laurdan, we evaluated in liposomes if the higher rigidity of the membrane caused by Al3+ can alter membrane phase state and/or hydration, and the relation of this effect to Al3+-stimulated lipid oxidation. In liposomes of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylserine, Al3+ (10–100 μM) induced phase coexistence and displacement of Tm. In contrast, in liposomes of brain phosphatidylcholine and brain phosphatidylserine, Al3+ (10–200 μM) did not affect membrane phase state but increased Laurdan generalized polarization (GP = −0.04 and 0.09 in the absence and presence of 200 μM Al3+, respectively). Sc3+, Ga3+, Be2+, Y3+, and La3+ also increased GP values, with an effect equivalent to a decrease in membrane temperature between 10 and 20°C. GP values in the presence of the cations were significantly correlated (r2 = 0.98, P < 0.001) with their capacity to stimulate Fe2+-initiated lipid oxidation. Metal-promoted membrane dehydration did not correlate with ability to enhance lipid oxidation, indicating that dehydration of the phospholipid polar headgroup is not a mechanism involved in cation-mediated enhancement of Fe2+-initiated lipid oxidation. Results indicate that changes in membrane phospholipid phase state favoring the displacement to gel state can facilitate the propagation of lipid oxidation.