Interactions of Al(acac)(3) with cell membranes and model phospholipid bilayers

Aluminum is a neurotoxic agent: however, little information has been obtain ed regarding its molecular cytotoxicity and the effects on the stability of biological membranes. This is mainly due to the ill-defined chemical speci ation of the metal compounds. For this reason, the present study used alumi num acetylacetonate, ( Al (acac)(3)) , a neutral, chemically well-defined, hydrolytically stable and lipophilic compound. To understand the molecular mechanism of its interaction with cell membranes, Al(acac)(3) was incubated with human erythrocytes, isolated toad shin and molecular models of biomem branes. The latter consisted of multilayers of dimyristoylphosphatidylcholi ne (DMPC) and dimyristoyphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. The results showed that Al(acac)(3) in teracted with the erythrocyte membrane modifying its normal discoid morphol ogy to both echinocytic and stomatocytic shapes. This finding indicates tha t the Al complex was inserted in both the outer and inner layers of the red cell membrane, a conclusion supported by X-ray diffraction analyses of DMP C and DMPE bilayers. Electrophysiological measurements performed on toad sk in revealed a significant decrease in the potential difference and short-ci rcuit current responses after application of Al(acac), effects interpreted to reflect inhibition of the active transport of ions. Al(acac), was active on both surfaces of the shin suggesting that the membrane was permeated by the metal complex. It is concluded that Al(acac)(3) both alters the molecu lar structure of the lipid bilayer. thereby modifying the biophysical prope rties of the cell membrane, and changes its physiological properties. (C) 1 999 Elsevier Science Inc. All rights reserved.