Interaction of the third helix of Antennapedia homeodomain and a phospholipid monolayer, studied by ellipsometry and PM-IRRAS at the air-water interface

The penetratin peptide, a 16 amino acid sequence extracted from Antennapedi a homeodomain, is able to translocate across a neural cell membrane through an unknown mechanism, most likely a non-specific interaction with membrane lipids. Beyond its potential application as vector targeting small hydroph ilic molecules and enabling them to reach a cell nucleus, this observation raises intriguing questions concerning the physico-chemistry of peptide-lip id interactions. Here we present a study of the role of lipid surface press ure and head charge on the mechanism of interaction. This was performed usi ng optical techniques: surface infrared spectroscopy and ellipsometry, appl ied to a monolayer of phospholipids deposited at the air-water interface. D etermination of the structure and orientation of peptides and lipids (separ ately or together) evidenced that electrostatic rather than amphiphilic int eractions determine the peptide adsorption and its action on lipids. (C) 20 00 Elsevier Science B.V. All rights reserved.