| dc.description.abstract | Antimicrobial peptides are important players in the immune systems and exert their influences mainly through their interactions with biomembranes. Due to their high efficiency in killing diverse invading molecules/organisms and low vulnerability to the drug resistance, antimicrobial peptides have drawn considerable attention and been regarded as promising candidates for the therapeutics of next generation. In order to improve our understanding toward the mechanisms underlying the interactions between antimicrobial peptides and biomembranes, this thesis work studied how the amino acid enriched in antimicrobial peptides, arginine, affects the physical and structural properties of phospholipid self-assemblies. Four types of poly-arginine peptides, R6, R9, R6C and R9C, were chosen for this study to scrutinize how the peptide chain length and the addition of the amino acid, cysteine, to the C-termini of the peptides modulate the properties of a phospholipid self-assembly. Two self-assembled structures were prepared for our research: First, the inverted hexagonal phase, prepared with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) was required for the small-angle X-ray scattering (SAXS) measurements of the elastic properties; second, 24 mol% DOPE/72 mol% 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/4 mol% 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate (DOPA) were used to prepare the cell membrane-mimicking liposomes (unilamellar vesicle), with their membrane thickness and structural stability investigated in order to extract the information on how the peptides interact with cell membranes. Our experimental results indicate that the presence of R6, R9 and R6C decreased the spontaneous curvature (an elastic property, which quantified the tendency of forming nonlamellar phases of a lipid) of DOPE, whereas the bending modulus (another elastic property, which described how hard the membrane is against bending) of DOPE was increased (i.e., the phospholipid self-assembly was stiffened) upon the addition of R9 and decreased (i.e., the phospholipid self-assembly was softened) upon the addition of R6 and R6C. Based on our results, we conclude: (1) Poly-arginine peptides have considerable interactions with DOPE even though the peptides carry no hydrophobic residue and the lipid self-assembly is electrostatically neutral (both of which point to the lack of attractive forces between the peptides and the self-assemblies); (2) how the different poly-arginine peptides modulate the spontaneous curvature and the bending modulus is speculated to depend on the insertion depths into the lipid self-assemblies of the peptides; (3) different underlying mechanisms may be employed by the poly-arginine peptides of different chain lengths to disrupt the structures of liposomes. | en_US |