title: Amphiphilic poly(phenyleneethynylene)s can mimic antimicrobial peptide membrane disordering effect by membrane insertion.
abstract: Antimicrobial peptides (AMPs) are a class of peptides that are innate to various organisms and function as a defense agent against harmful microorganisms by means of membrane disordering. Characteristic chemical and structural properties of AMPs allow selective interaction and subsequent disruption of invaders' cell membranes. Polymers based on m-phenylene ethynylenes (mPE) were designed and synthesized to mimic the amphiphilic, cationic, and rigid structure of AMPs and were found to be good mimics of AMPs in terms of their high potency toward microbes and low hemolytic activities. Using a Langmuir monolayer insertion assay, two mPEs are found to readily insert into anionic model bacterial membranes but to differ in the degree of selectivity between bacterial and mammalian erythrocyte model membranes. Comparison of grazing incidence X-ray diffraction (GIXD) data before and after the insertion of mPE clearly indicates that the insertion of mPE disrupts lipid packing, altering the tilt of the lipid tail. X-ray reflectivity (XR) measurements of the lipid/mPE system demonstrate that mPE molecules insert through the headgroup region and partially into the tail group region, thus accounting for the observed disordering of tail packing. This study demonstrates that mPEs can mimic AMP's membrane disordering.
authors.affiliation: Department of Chemistry, the Institute for Biophysical Dynamics & the James Franck Institute, the University of Chicago, Illinois 60637, USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishitsuka
authors.forename: Lachelle
authors.initials: L
authors.lastname: Arnt
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Majewski
authors.forename: Shelli
authors.initials: S
authors.lastname: Frey
authors.forename: Maria
authors.initials: M
authors.lastname: Ratajczek
authors.forename: Kristian
authors.initials: K
authors.lastname: Kjaer
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Tew
authors.forename: Ka Yee C
authors.initials: KY
authors.lastname: Lee
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000480:Alkynes / Q000737:chemistry* / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D040761:Biomimetic Materials / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004987:Ethers / Q000737:chemistry* / Q000494:pharmacology; D006461:Hemolysis; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D010715:Phosphatidylglycerols / Q000737:chemistry; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry
chemical_list: D000480:Alkynes; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D004987:Ethers; D008563:Membrane Lipids; D010715:Phosphatidylglycerols; D011506:Proteins; C436384:phenyleneethynylene; C094880:protegrin-1; D015060:1,2-Dipalmitoylphosphatidylcholine; C030345:1,2-dipalmitoylphosphatidylglycerol