Studies of amphiphilic helical peptides interacting with lipid bilayer membranes by x-ray and neutron scattering
Huang, Huey W.
Doctor of Philosophy
A variety of amphiphilic helical peptides have been shown to exhibit a transition from adsorbing parallel to a membrane surface at low concentrations to inserting perpendicularly into the membrane at high concentrations. This transition has been correlated to the peptides' cytolytic activities. Alamethicin, a 20 amino acid peptide, is an example of an amphiphilic helical peptide. Previous studies of alamethicin in diphytanoyl phosphatidylcoline (DPhPC) lipid bilayers showed that alamethicin were adsorbed in the lipid polar region at low concentrations. X-ray diffraction experiments showed that the bilayer thickness of DPhPC decreased with increasing alamethicin concentration in proportion to the peptide lipid molar ratio from 1/150 to 1/47 (Wu et al., 1995); the latter is near the threshold of the critical concentration for insertion, 1/40. This thesis will focus on the high concentration states of alamethicin in lipid bilayers. A new technique of x-ray and neutron in-plane scattering is described. With neutron in-plane scattering, the aqueous pores ($\ge20$A in diameter) formed by inserted alamethicin in lipid bilayers were directly observed. DPhPC with alamethicin at concentrations above the critical concentration for insertion was studied by x-ray lamellar diffraction. The bilayer thickness of DPhPC first decreases as the peptide begins to insert and then increases after a substantial fraction of the peptide is inserted. Huang (1995) speculated that the peptide insertion transition was caused by the membrane deformation energy. This idea is extended to the high concentration region and is used to explain qualitatively the mechanics of the peptide insertion transition.
Biophysics; Molecular chemistry