On the Mechanism of How the Antimicrobial-Competent Peptides Dictate the Elastic Properties and Structural Integrity of Lipid Membranes
| Autor: | Si-Han Chen, 陳思翰 |
|---|---|
| Rok vydání: | 2016 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 104 Antimicrobial peptides are important players in the immune systems all across the biological spectrum. These peptides exert their influences mainly through their interactions with biomembranes rather than with specific proteins as for conventional antibiotics. This feature, along with the difference in the membrane compositions, makes human cells (e.g., blood cells) free from being the targets of the peptides, posing the peptides as promising candidates for the therapeutics of next generation. To understand how the peptides interact with the biomembranes of pathogens and human cells differentially, we investigate how the variations in the amino acid (AA) sequence and length of an antimicrobial-competent peptide dictate its influences on the elastic properties and structural integrity of a lipid membrane, with the AAs enriched in common antimicrobial peptides, the acidic lysine (K) and hydrophobic tryptophan (W), used to construct a family of artificial peptides. It is found that while peptides purely made of lysine has essentially no influence on the properties of an electrically neutral lipid membrane, incorporating tryptophan to the peptides endows them the capability to modulate the elastic properties and disrupt the structural integrity of the membrane. The discrepancy might arise from the fact that the tryptophan side chain prefers being located on the polar/apolar interface, which elevates the elastic energy of the membrane and thus energetically favors the formation of curved structures (e.g., pore). On the contrary, all the studied peptides, regardless of their AA sequences, lose their capability to affect the elastic properties of a membrane when the membrane contains acidic lipids. We speculate that the strong electrostatic force, which secures the peptides on the membrane surface rather than allowing them to move deep into the polar/apolar interface, is responsible for the phenomenon. It is therefore concluded that the electrostatic force is the dominant factor in the interactions between the peptides and lipid membranes studied here, whereas the hydrophobic interaction and hydrogen bonding are secondary to the electrostatic force in this respect. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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