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

Abstract

Aluminum is a neurotoxic agent; however, little information has been obtained regarding its molecular cytotoxicity and the effects on the stability of biological membranes. This is mainly due to the ill-defined chemical speciation of the metal compounds. For this reason, the present study used aluminum 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 skin and molecular models of biomembranes. The latter consisted of multilayers of dimyristoylphosphatidylcholine (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 interacted with the erythrocyte membrane modifying its normal discoid morphology to both echinocytic and stomatocytic shapes. This finding indicates that 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 DMPC and DMPE bilayers. Electrophysiological measurements performed on toad skin revealed a significant decrease in the potential difference and short-circuit current responses after application of Al(acac)3, effects interpreted to reflect inhibition of the active transport of ions. Al(acac)3 was active on both surfaces of the skin suggesting that the membrane was permeated by the metal complex. It is concluded that Al(acac)3 both alters the molecular structure of the lipid bilayer, thereby modifying the biophysical properties of the cell membrane, and changes its physiological properties.