Amyloid beta-protein (A beta) has been reported to interact with a variety of lipid species, although the thermodynamic driving force remains unclear. We investigated the binding of A beta s labeled with the dye diethylaminocoumarin (DAC-A beta s) to lipid bilayers under various conditions. DAC-A beta-(1-40) electrostatically bound to anionic and cationic lipids at acidic and alkaline interfacial pH, respectively. However, at neutral pH, electroneutral A beta did not bind to these lipids, indicating little hydrophobic interaction between A beta-(1-40) and the acyl chains of lipids. In contrast, DAC-A beta associated with glycolipids even under electroneutral conditions. These results suggested that hydrogen-bonding as well as hydrophobic interactions with sugar groups of glycolipids drive the membrane binding of A beta-(1-40). (C) 2008 Elsevier Inc. All rights reserved.