title: Pore formation in 1,2-dimyristoyl-sn-glycero-3-phosphocholine/cholesterol mixed bilayers by low concentrations of antimicrobial peptide melittin.
abstract: Antimicrobial peptides (AMP) represent a class of compounds to combat antibiotic resistance to microorganisms, neutralize biological warfare agents, and as topical antimicrobial agents. AMP kills microbial cells through insertion and permeabilization of the cytoplasmic membranes. It is important to predict the efficacy of AMP at low concentration to circumvent their toxicity. Leakage of fluorescent dyes (calcein, FD4 and FD20) of different molecular weights entrapped within 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/cholesterol mixed liposomes by AMP melittin indicated (i) a critical melittin concentration for pore formation and (ii) a lag time for pore formation above this critical concentration. The lag time decreased with an increase in melittin concentration and was in the order FD20>FD4>calcein. % α helix of melittin increased when exposed to liposome with this increase being more pronounced at higher concentrations eventually reaching an asymptotic value. The rate of dye leakage following the lag time was found to be larger at higher melittin concentration. A simplified mathematical model for nucleation and growth of pores formed by an aggregate of melittin in lipid bilayer is proposed to predict the variation of rate of dye leakage with melittin concentration which agreed fairly well with the data for calcein and seems to suggest a toroidal mechanism of pore formation with participation of large number of phospholipid heads.
authors.affiliation: Department of Applied Chemistry, College of science, China Agriculture University, 2 Yuanmingyuan Xilu, Haidian Dist., Beijing 100193, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA. Electronic address: narsimha@purdue.edu.
authors.forename: Ganesan
authors.initials: G
authors.lastname: Narsimhan
authors.affiliation: Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Xiayou
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Applied Chemistry, College of science, China Agriculture University, 2 Yuanmingyuan Xilu, Haidian Dist., Beijing 100193, China.
authors.forename: Fengpei
authors.initials: F
authors.lastname: Du
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008555:Melitten / Q000737:chemistry*; D010767:Phosphorylcholine
chemical_list: D000890:Anti-Infective Agents; D008051:Lipid Bilayers; D010767:Phosphorylcholine; D008555:Melitten; D002784:Cholesterol
keywords: Antimicrobial peptide; Cholesterol; DMPC; Lag time; Lipid bilayer; Melittin; Pore formation