Antimicrobial peptides (AMPs) are relatively-short chain molecules that living organisms
use to defend themselves against a wide range of invading microorganisms such as
bacteria and viruses. They selectively bind to and kill microbes over host cells by permeabilizing
cell membranes or by inhibiting the biological functions of intra-cellular components.
Despite its significance in determining their cell selectivity, however, the cell-concentration
dependence of AMP's membrane-perturbing activity has not been criticality examined.
In this thesis, we present a physical model for cell selectivity of AMPs, especially its
cell-concentration dependence. To this end, we use a coarse-grained model that captures
essential molecular details such as lipid composition (e.g., fraction of anionic lipids) and
peptide amphiphilicity and charge. In particular, we calculate the surface coverage of peptides
in the membrane-perturbing mode as a function of peptide and cell densities: those
that bind to the interface between lipid headgroups and tails. This allows us to extract
the minimum inhibitory concentration (MIC) and the minimum hemolytic concentration
(MHC) of the peptides. Our results show that both MIC and MHC increase as the cell density
increases so that the peptide selectivity (given by MHC/MIC) decreases with increasing
cell density. Our results will help resolve conflicting interpretations of peptide-selectivity
experiments.
| Identifer | oai:union.ndltd.org:WATERLOO/oai:uwspace.uwaterloo.ca:10012/7631 |
| Date | 14 June 2013 |
| Creators | Bagheri, Azadeh |
| Source Sets | University of Waterloo Electronic Theses Repository |
| Language | English |
| Detected Language | English |
| Type | Thesis or Dissertation |
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