| Summary: | 博士 === 國立中央大學 === 物理研究所 === 92 === Abstract
When membrane surface adsorbs antimicrobial peptides, stable pores are found to emerge if the adsorbed peptides are sufficiently dense. This thesis presents both experimental and theoretical approaches to the understanding of such pore formation induced by antimicrobial peptides.
When binding to membrane surface, antimicrobial peptides exhibit amphiphilic structure and embed themselves into the headgroup region of the membrane. As a result, the hydrophobic (carbon chain) region of the membrane is surface-stretched or equivalently is thinning. Based on the fact that the thinning effect is increased with peptide concentration, we proposed a theory to show: 1. The membrane thinning in high peptide concentration can be sufficiently strong to make pores on membrane; 2. The pores can be stabilized by transferring a fraction of peptides to the pore wall, resembling as a phase transition.
Experimentally, we investigated the pore formation process in model bilayer membranes of various lipid compositions. Two of the best-study peptides, alamethicin and melittin, were used to represent peptides making two different types of pores, that is, barrel-stave pores and toroidal pores. Two methods were employed in experiments. They are: 1. Oriented circular dichroism (OCD) to monitor the peptide orientation, either parallel (surface adsorbed) or perpendicular (pore wall adsorbed), to the membrane surface; 2. Lamellar x-ray diffraction (LXD) to measure the membrane bilayer thickness. Experiments were conducted to measure the peptide orientation and the membrane thickness as a function of peptide concentration.
All experimental results were in agreement with the prediction of the proposed theory. The parameters that characterize the peptide-membrane interaction related to the pore formation were extracted from the experimental results. We discussed the meaning of these parameters and compared their values for different lipids and for the two different types of pores. These parameters are useful for further molecular analysis and are excellent targets for molecular dynamic simulations studies. The results in this thesis are also potentially useful for gene and drug deliveries, drug design and anti-infective therapeutics.
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