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Study of the Interaction of a Novel Semi-Synthetic Peptide with Model Lipid Membranes

Most linear peptides directly interact with membranes, but the mechanisms of interaction are far from being completely understood. Here, we present an investigation of the membrane interactions of a designed peptide containing a non-natural, synthetic amino acid. We selected a nonapeptide that is re...

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Autores principales: Sessa, Lucia, Concilio, Simona, Walde, Peter, Robinson, Tom, Dittrich, Petra S., Porta, Amalia, Panunzi, Barbara, Caruso, Ugo, Piotto, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603383/
https://www.ncbi.nlm.nih.gov/pubmed/33086635
http://dx.doi.org/10.3390/membranes10100294
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author Sessa, Lucia
Concilio, Simona
Walde, Peter
Robinson, Tom
Dittrich, Petra S.
Porta, Amalia
Panunzi, Barbara
Caruso, Ugo
Piotto, Stefano
author_facet Sessa, Lucia
Concilio, Simona
Walde, Peter
Robinson, Tom
Dittrich, Petra S.
Porta, Amalia
Panunzi, Barbara
Caruso, Ugo
Piotto, Stefano
author_sort Sessa, Lucia
collection PubMed
description Most linear peptides directly interact with membranes, but the mechanisms of interaction are far from being completely understood. Here, we present an investigation of the membrane interactions of a designed peptide containing a non-natural, synthetic amino acid. We selected a nonapeptide that is reported to interact with phospholipid membranes, ALYLAIRKR, abbreviated as ALY. We designed a modified peptide (azoALY) by substituting the tyrosine residue of ALY with an antimicrobial azobenzene-bearing amino acid. Both of the peptides were examined for their ability to interact with model membranes, assessing the penetration of phospholipid monolayers, and leakage across the bilayer of large unilamellar vesicles (LUVs) and giant unilamellar vesicles (GUVs). The latter was performed in a microfluidic device in order to study the kinetics of leakage of entrapped calcein from the vesicles at the single vesicle level. Both types of vesicles were prepared from a 9:1 (mol/mol) mixture of POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho(1′-rac-glycerol). Calcein leakage from the vesicles was more pronounced at a low concentration in the case of azoALY than for ALY. Increased vesicle membrane disturbance in the presence of azoALY was also evident from an enzymatic assay with LUVs and entrapped horseradish peroxidase. Molecular dynamics simulations of ALY and azoALY in an anionic POPC/POPG model bilayer showed that ALY peptide only interacts with the lipid head groups. In contrast, azoALY penetrates the hydrophobic core of the bilayers causing a stronger membrane perturbation as compared to ALY, in qualitative agreement with the experimental results from the leakage assays.
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spelling pubmed-76033832020-11-01 Study of the Interaction of a Novel Semi-Synthetic Peptide with Model Lipid Membranes Sessa, Lucia Concilio, Simona Walde, Peter Robinson, Tom Dittrich, Petra S. Porta, Amalia Panunzi, Barbara Caruso, Ugo Piotto, Stefano Membranes (Basel) Article Most linear peptides directly interact with membranes, but the mechanisms of interaction are far from being completely understood. Here, we present an investigation of the membrane interactions of a designed peptide containing a non-natural, synthetic amino acid. We selected a nonapeptide that is reported to interact with phospholipid membranes, ALYLAIRKR, abbreviated as ALY. We designed a modified peptide (azoALY) by substituting the tyrosine residue of ALY with an antimicrobial azobenzene-bearing amino acid. Both of the peptides were examined for their ability to interact with model membranes, assessing the penetration of phospholipid monolayers, and leakage across the bilayer of large unilamellar vesicles (LUVs) and giant unilamellar vesicles (GUVs). The latter was performed in a microfluidic device in order to study the kinetics of leakage of entrapped calcein from the vesicles at the single vesicle level. Both types of vesicles were prepared from a 9:1 (mol/mol) mixture of POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho(1′-rac-glycerol). Calcein leakage from the vesicles was more pronounced at a low concentration in the case of azoALY than for ALY. Increased vesicle membrane disturbance in the presence of azoALY was also evident from an enzymatic assay with LUVs and entrapped horseradish peroxidase. Molecular dynamics simulations of ALY and azoALY in an anionic POPC/POPG model bilayer showed that ALY peptide only interacts with the lipid head groups. In contrast, azoALY penetrates the hydrophobic core of the bilayers causing a stronger membrane perturbation as compared to ALY, in qualitative agreement with the experimental results from the leakage assays. MDPI 2020-10-19 /pmc/articles/PMC7603383/ /pubmed/33086635 http://dx.doi.org/10.3390/membranes10100294 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sessa, Lucia
Concilio, Simona
Walde, Peter
Robinson, Tom
Dittrich, Petra S.
Porta, Amalia
Panunzi, Barbara
Caruso, Ugo
Piotto, Stefano
Study of the Interaction of a Novel Semi-Synthetic Peptide with Model Lipid Membranes
title Study of the Interaction of a Novel Semi-Synthetic Peptide with Model Lipid Membranes
title_full Study of the Interaction of a Novel Semi-Synthetic Peptide with Model Lipid Membranes
title_fullStr Study of the Interaction of a Novel Semi-Synthetic Peptide with Model Lipid Membranes
title_full_unstemmed Study of the Interaction of a Novel Semi-Synthetic Peptide with Model Lipid Membranes
title_short Study of the Interaction of a Novel Semi-Synthetic Peptide with Model Lipid Membranes
title_sort study of the interaction of a novel semi-synthetic peptide with model lipid membranes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603383/
https://www.ncbi.nlm.nih.gov/pubmed/33086635
http://dx.doi.org/10.3390/membranes10100294
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