ANTIMICROBIAL PEPTIDES IN MODEL MEMBRANES STUDIED BY IN-PLANE NEUTRON SCATTERING. D.L. Worcester*, Ke He, S.J. Ludtke, W.T. Heller, T. Harroun and H. W Huang, Rice University, Houston, TX 77251-1892 and *University of Missouri, Columbia, MO 65211.

Antimicrobial peptides isolated from the host defense systems of organisms have been shown to exert their activity directly on cell membranes, but the antimicrobial mechanisms have not been elucidated, partly because the large quaternary structures formed by these peptides in membranes are difficult to establish. Many of these peptides insert into the membrane as transmembrane alpha helices when their concentrations exceed a lipid-dependent critical value. Organization of many of these peptide helices together with membrane lipid into special structures is probably a key aspect of antimicrobial action. We are using neutron in-plane scattering to elucidate these structures for several antimicrobial peptides. Using this technique we show that inserted alamethicin creates aqueous pores in membranes. Neutron data were collected for alamethicin in DLPC, deuterated DLPC and DPhPC with D2O or H2O. Alamethicin appears to form pores in the barrel-stave fashion. Calculated form factors for the pores with different deuteration conditions multiplied by a simulated structure factor, were used to fit the in-plane neutron scattering data and establish pore size as well as number density. Essentially all of the inserted alamethicin was found to be in the form of pores. Other antimicrobial peptides have also been measured with this in-plane neutron scattering technique. Results for magainin show very detailed, temperature dependent, in-plane scattering. Structures other than pores of the barrel-stave type may be present for some of the peptides.