Comparative interaction of α-helical and β-sheet amphiphilic isopeptides with phospholipid monolayers

The two sequential amphiphilic peptide isomers, (Leu-Lys-Lys-Leu)(4) and (Leu-Lys)(8), were chosen as models for alpha -helical and beta -sheet peptides, respectively. In order to evaluate the contribution of the secondary structure of a peptide to its penetration into cellular membranes, interactions of these isopeptides with L-alpha -dimyristoyl phosphatidylcholine (DMPC) monolayers were studied. Both isopeptides penetrate into DMPC monolayers up to an exclusion pressure of similar to 27 mN/m, but a discontinuity is observed in the penetration profile of the alpha -helical (LKKL)(4). The main parameters extracted from the compression isotherms of the mixed peptide/DMPC monolayers-namely,, transition pressure, mean area. elasticity modulus, and energy of mixing-were analyzed. These analyses indicate that the alpha -helical isomer interacts strongly with DMPC by forming a 1:32 (LKKL)(4)-DMPC complex. When engaged in this complex, (LKKL)(4) behaves as an hydrophobic helix and has a tendency to become vertically oriented in the course of the compression process. The beta -sheet (LK)(8) interacts more weakly with DMPC and no complex can be detected. (C) 2001 John Wiley & Sons, Inc.