Physical Model for Cell Selectivity of Antimicrobial Peptides

Antimicrobial peptide;cell selectivity;Physics

Bagheri, Azadeh

University of Waterloo

关键词: Antimicrobial peptide;    cell selectivity;    Physics;   

Others  :  https://uwspace.uwaterloo.ca/bitstream/10012/7631/1/Bagheri_Azadeh.pdf

瑞士|英语

来源: UWSPACE Waterloo Institutional Repository

【 摘 要 】

Antimicrobial peptides (AMPs) are relatively-short chain molecules that living organismsuse to defend themselves against a wide range of invading microorganisms such asbacteria and viruses. They selectively bind to and kill microbes over host cells by permeabilizingcell membranes or by inhibiting the biological functions of intra-cellular components.Despite its significance in determining their cell selectivity, however, the cell-concentrationdependence 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 itscell-concentration dependence. To this end, we use a coarse-grained model that capturesessential molecular details such as lipid composition (e.g., fraction of anionic lipids) andpeptide amphiphilicity and charge. In particular, we calculate the surface coverage of peptidesin the membrane-perturbing mode as a function of peptide and cell densities: thosethat bind to the interface between lipid headgroups and tails. This allows us to extractthe 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 densityincreases so that the peptide selectivity (given by MHC/MIC) decreases with increasingcell density. Our results will help resolve conflicting interpretations of peptide-selectivityexperiments.