title: Role of cationic group structure in membrane binding and disruption by amphiphilic copolymers.
abstract: Cationic, amphiphilic polymers are currently being used as antimicrobial agents that disrupt biomembranes, although their mechanisms remain poorly understood. Herein, membrane association and disruption by amphiphilic polymers bearing primary, tertiary, or quaternary ammonium salt groups reveal the role of cationic group structure in the polymer-membrane interaction. The dissociation constants of polymers to liposomes of POPC were obtained by a fluorometric assay, exploiting the environmental sensitivity of dansyl moieties in the polymer end groups. Dye leakage from liposomes and solid-state NMR provided further insights into the polymer-induced membrane disruption. Interestingly, the polymers with primary amine groups induced reorganization of the bilayer structure to align lipid headgroups perpendicular to the membrane. The results showed that polymers bearing primary amines exceed the tertiary and quaternary ammonium counterparts in membrane binding and disrupting abilities. This is likely due to enhanced complexation of primary amines to the phosphate groups in the lipids, through a combination of hydrogen bonding and electrostatic interactions.
authors.affiliation: Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Edmund F
authors.initials: EF
authors.lastname: Palermo
authors.forename: Dong-Kuk
authors.initials: DK
authors.lastname: Lee
authors.forename: Ayyalusamy
authors.initials: A
authors.lastname: Ramamoorthy
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kuroda
mesh_terms: D000588:Amines / Q000737:chemistry; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D002412:Cations / Q000737:chemistry; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods; D005456:Fluorescent Dyes / Q000032:analysis; D005470:Fluorometry; D006860:Hydrogen Bonding; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D010710:Phosphates / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000378:metabolism; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013501:Surface-Active Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000588:Amines; D000890:Anti-Infective Agents; D002412:Cations; D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D008081:Liposomes; D010710:Phosphates; D010713:Phosphatidylcholines; D011108:Polymers; D000644:Quaternary Ammonium Compounds; D013501:Surface-Active Agents; C028694:1-palmitoyl-2-oleoylphosphatidylcholine