Arginine-Containing Surfactant-Like Peptides: Interaction with Lipid Membranes and Antimicrobial Activity

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Arginine-Containing Surfactant-Like Peptides : Interaction with Lipid Membranes and Antimicrobial Activity. / Castelletto, Valeria; Barnes, Ruth H.; Karatzas, Kimon-Andreas; Edwards-Gayle, Charlotte J. C.; Greco, Francesca; Hamley, Ian W.; Rambo, Robert; Seitsonen, Jani; Ruokolainen, Janne.

In: Biomacromolecules, Vol. 19, No. 7, 07.2018, p. 2782-2794.

Research output: Contribution to journalArticleScientificpeer-review

Harvard

Castelletto, V, Barnes, RH, Karatzas, K-A, Edwards-Gayle, CJC, Greco, F, Hamley, IW, Rambo, R, Seitsonen, J & Ruokolainen, J 2018, 'Arginine-Containing Surfactant-Like Peptides: Interaction with Lipid Membranes and Antimicrobial Activity' Biomacromolecules, vol. 19, no. 7, pp. 2782-2794. https://doi.org/10.1021/acs.biomac.8b00391

APA

Castelletto, V., Barnes, R. H., Karatzas, K-A., Edwards-Gayle, C. J. C., Greco, F., Hamley, I. W., ... Ruokolainen, J. (2018). Arginine-Containing Surfactant-Like Peptides: Interaction with Lipid Membranes and Antimicrobial Activity. Biomacromolecules, 19(7), 2782-2794. https://doi.org/10.1021/acs.biomac.8b00391

Vancouver

Castelletto V, Barnes RH, Karatzas K-A, Edwards-Gayle CJC, Greco F, Hamley IW et al. Arginine-Containing Surfactant-Like Peptides: Interaction with Lipid Membranes and Antimicrobial Activity. Biomacromolecules. 2018 Jul;19(7):2782-2794. https://doi.org/10.1021/acs.biomac.8b00391

Author

Castelletto, Valeria ; Barnes, Ruth H. ; Karatzas, Kimon-Andreas ; Edwards-Gayle, Charlotte J. C. ; Greco, Francesca ; Hamley, Ian W. ; Rambo, Robert ; Seitsonen, Jani ; Ruokolainen, Janne. / Arginine-Containing Surfactant-Like Peptides : Interaction with Lipid Membranes and Antimicrobial Activity. In: Biomacromolecules. 2018 ; Vol. 19, No. 7. pp. 2782-2794.

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@article{c910913057394e3c9369fbd5fd3de1f2,
title = "Arginine-Containing Surfactant-Like Peptides: Interaction with Lipid Membranes and Antimicrobial Activity",
abstract = "The activity of antimicrobial peptides stems from their interaction with bacterial membranes, which are disrupted according to a number of proposed mechanisms. Here, we investigate the interaction of a model antimicrobial peptide that contains a single arginine residue with vesicles containing model lipid membranes. The surfactant-like peptide Ala(6)-Arg (A(6)R) is studied in the form where both termini are capped (CONH-A(6)R-NH2, capA(6)R) or uncapped (NH2-A(6)R-OH, A(6)R). Lipid membranes are selected to correspond to model anionic membranes (POPE/POPG) resembling those in bacteria or model zwitterionic membranes (POPC/DOPC) similar to those found in mammalian cells. Viable antimicrobial agents should show activity against anionic membranes but not zwitterionic membranes. We find, using small-angle X-ray scattering (SAXS) and cryogenic-TEM (transmission electron microscopy) that, uniquely, capA(6)R causes structuring of anionic membranes due to the incorporation of the peptide in the lipid bilayer with peptide beta-sheet conformation revealed by circular dichroism spectroscopy (CD). There is a preferential interaction of the peptide with POPG (which is the only anionic lipid in the systems studied) due to electrostatic interactions and bidentate hydrogen bonding between arginine guanidinium and lipid phosphate groups. At a certain composition, this peptide leads to the remarkable tubulation of zwitterionic phosphatidylcholine (PC) vesicles, which is ascribed to the interaction of the peptide with the outer lipid membrane, which occurs without penetration into the membrane. In contrast, peptide A(6)R has a minimal influence on the anionic lipid membranes (and no beta-sheet peptide structure is observed) but causes thinning (lamellar decorrelation) of zwitterionic membranes. We also investigated the cytotoxicity (to fibroblasts) and antimicrobial activity of these two peptides against model Gram positive and Gram negative bacteria. A strong selective antimicrobial activity against Gram positive Listeria monocytogenes, which is an important food-borne pathogen, is observed for capA(6)R. Peptide A(6)R is active against all three studied bacteria. The activity of the peptides against bacteria and mammalian cells is related to the specific interactions uncovered through our SAXS, cryo-TEM, and CD measurements. Our results highlight the exquisite sensitivity to the charge distribution in these designed peptides and its effect on the interaction with lipid membranes bearing different charges, and ultimately on antimicrobial activity.",
keywords = "LISTERIA-MONOCYTOGENES LO28, ANTIBACTERIAL ACTIVITIES, SHAPE TRANSFORMATIONS, AMPHIPHILIC PEPTIDES, SECONDARY STRUCTURE, MECHANISMS, VESICLES, ACID, RESISTANCE, DESTABILIZATION",
author = "Valeria Castelletto and Barnes, {Ruth H.} and Kimon-Andreas Karatzas and Edwards-Gayle, {Charlotte J. C.} and Francesca Greco and Hamley, {Ian W.} and Robert Rambo and Jani Seitsonen and Janne Ruokolainen",
year = "2018",
month = "7",
doi = "10.1021/acs.biomac.8b00391",
language = "English",
volume = "19",
pages = "2782--2794",
journal = "Biomacromolecules",
issn = "1525-7797",
publisher = "AMERICAN CHEMICAL SOCIETY",
number = "7",

}

RIS - Download

TY - JOUR

T1 - Arginine-Containing Surfactant-Like Peptides

T2 - Interaction with Lipid Membranes and Antimicrobial Activity

AU - Castelletto, Valeria

AU - Barnes, Ruth H.

AU - Karatzas, Kimon-Andreas

AU - Edwards-Gayle, Charlotte J. C.

AU - Greco, Francesca

AU - Hamley, Ian W.

AU - Rambo, Robert

AU - Seitsonen, Jani

AU - Ruokolainen, Janne

PY - 2018/7

Y1 - 2018/7

N2 - The activity of antimicrobial peptides stems from their interaction with bacterial membranes, which are disrupted according to a number of proposed mechanisms. Here, we investigate the interaction of a model antimicrobial peptide that contains a single arginine residue with vesicles containing model lipid membranes. The surfactant-like peptide Ala(6)-Arg (A(6)R) is studied in the form where both termini are capped (CONH-A(6)R-NH2, capA(6)R) or uncapped (NH2-A(6)R-OH, A(6)R). Lipid membranes are selected to correspond to model anionic membranes (POPE/POPG) resembling those in bacteria or model zwitterionic membranes (POPC/DOPC) similar to those found in mammalian cells. Viable antimicrobial agents should show activity against anionic membranes but not zwitterionic membranes. We find, using small-angle X-ray scattering (SAXS) and cryogenic-TEM (transmission electron microscopy) that, uniquely, capA(6)R causes structuring of anionic membranes due to the incorporation of the peptide in the lipid bilayer with peptide beta-sheet conformation revealed by circular dichroism spectroscopy (CD). There is a preferential interaction of the peptide with POPG (which is the only anionic lipid in the systems studied) due to electrostatic interactions and bidentate hydrogen bonding between arginine guanidinium and lipid phosphate groups. At a certain composition, this peptide leads to the remarkable tubulation of zwitterionic phosphatidylcholine (PC) vesicles, which is ascribed to the interaction of the peptide with the outer lipid membrane, which occurs without penetration into the membrane. In contrast, peptide A(6)R has a minimal influence on the anionic lipid membranes (and no beta-sheet peptide structure is observed) but causes thinning (lamellar decorrelation) of zwitterionic membranes. We also investigated the cytotoxicity (to fibroblasts) and antimicrobial activity of these two peptides against model Gram positive and Gram negative bacteria. A strong selective antimicrobial activity against Gram positive Listeria monocytogenes, which is an important food-borne pathogen, is observed for capA(6)R. Peptide A(6)R is active against all three studied bacteria. The activity of the peptides against bacteria and mammalian cells is related to the specific interactions uncovered through our SAXS, cryo-TEM, and CD measurements. Our results highlight the exquisite sensitivity to the charge distribution in these designed peptides and its effect on the interaction with lipid membranes bearing different charges, and ultimately on antimicrobial activity.

AB - The activity of antimicrobial peptides stems from their interaction with bacterial membranes, which are disrupted according to a number of proposed mechanisms. Here, we investigate the interaction of a model antimicrobial peptide that contains a single arginine residue with vesicles containing model lipid membranes. The surfactant-like peptide Ala(6)-Arg (A(6)R) is studied in the form where both termini are capped (CONH-A(6)R-NH2, capA(6)R) or uncapped (NH2-A(6)R-OH, A(6)R). Lipid membranes are selected to correspond to model anionic membranes (POPE/POPG) resembling those in bacteria or model zwitterionic membranes (POPC/DOPC) similar to those found in mammalian cells. Viable antimicrobial agents should show activity against anionic membranes but not zwitterionic membranes. We find, using small-angle X-ray scattering (SAXS) and cryogenic-TEM (transmission electron microscopy) that, uniquely, capA(6)R causes structuring of anionic membranes due to the incorporation of the peptide in the lipid bilayer with peptide beta-sheet conformation revealed by circular dichroism spectroscopy (CD). There is a preferential interaction of the peptide with POPG (which is the only anionic lipid in the systems studied) due to electrostatic interactions and bidentate hydrogen bonding between arginine guanidinium and lipid phosphate groups. At a certain composition, this peptide leads to the remarkable tubulation of zwitterionic phosphatidylcholine (PC) vesicles, which is ascribed to the interaction of the peptide with the outer lipid membrane, which occurs without penetration into the membrane. In contrast, peptide A(6)R has a minimal influence on the anionic lipid membranes (and no beta-sheet peptide structure is observed) but causes thinning (lamellar decorrelation) of zwitterionic membranes. We also investigated the cytotoxicity (to fibroblasts) and antimicrobial activity of these two peptides against model Gram positive and Gram negative bacteria. A strong selective antimicrobial activity against Gram positive Listeria monocytogenes, which is an important food-borne pathogen, is observed for capA(6)R. Peptide A(6)R is active against all three studied bacteria. The activity of the peptides against bacteria and mammalian cells is related to the specific interactions uncovered through our SAXS, cryo-TEM, and CD measurements. Our results highlight the exquisite sensitivity to the charge distribution in these designed peptides and its effect on the interaction with lipid membranes bearing different charges, and ultimately on antimicrobial activity.

KW - LISTERIA-MONOCYTOGENES LO28

KW - ANTIBACTERIAL ACTIVITIES

KW - SHAPE TRANSFORMATIONS

KW - AMPHIPHILIC PEPTIDES

KW - SECONDARY STRUCTURE

KW - MECHANISMS

KW - VESICLES

KW - ACID

KW - RESISTANCE

KW - DESTABILIZATION

U2 - 10.1021/acs.biomac.8b00391

DO - 10.1021/acs.biomac.8b00391

M3 - Article

VL - 19

SP - 2782

EP - 2794

JO - Biomacromolecules

JF - Biomacromolecules

SN - 1525-7797

IS - 7

ER -

ID: 27449639