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ZnO nanoparticles modulate the ionic transport and voltage regulation of lysenin nanochannels

BACKGROUND: The insufficient understanding of unintended biological impacts from nanomaterials (NMs) represents a serious impediment to their use for scientific, technological, and medical applications. While previous studies have focused on understanding nanotoxicity effects mostly resulting from c...

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Autores principales: Bryant, Sheenah L., Eixenberger, Josh E., Rossland, Steven, Apsley, Holly, Hoffmann, Connor, Shrestha, Nisha, McHugh, Michael, Punnoose, Alex, Fologea, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732404/
https://www.ncbi.nlm.nih.gov/pubmed/29246155
http://dx.doi.org/10.1186/s12951-017-0327-9
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author Bryant, Sheenah L.
Eixenberger, Josh E.
Rossland, Steven
Apsley, Holly
Hoffmann, Connor
Shrestha, Nisha
McHugh, Michael
Punnoose, Alex
Fologea, Daniel
author_facet Bryant, Sheenah L.
Eixenberger, Josh E.
Rossland, Steven
Apsley, Holly
Hoffmann, Connor
Shrestha, Nisha
McHugh, Michael
Punnoose, Alex
Fologea, Daniel
author_sort Bryant, Sheenah L.
collection PubMed
description BACKGROUND: The insufficient understanding of unintended biological impacts from nanomaterials (NMs) represents a serious impediment to their use for scientific, technological, and medical applications. While previous studies have focused on understanding nanotoxicity effects mostly resulting from cellular internalization, recent work indicates that NMs may interfere with transmembrane transport mechanisms, hence enabling contributions to nanotoxicity by affecting key biological activities dependent on transmembrane transport. In this line of inquiry, we investigated the effects of charged nanoparticles (NPs) on the transport properties of lysenin, a pore-forming toxin that shares fundamental features with ion channels such as regulation and high transport rate. RESULTS: The macroscopic conductance of lysenin channels greatly diminished in the presence of cationic ZnO NPs. The inhibitory effects were asymmetrical relative to the direction of the electric field and addition site, suggesting electrostatic interactions between ZnO NPs and a binding site. Similar changes in the macroscopic conductance were observed when lysenin channels were reconstituted in neutral lipid membranes, implicating protein-NP interactions as the major contributor to the reduced transport capabilities. In contrast, no inhibitory effects were observed in the presence of anionic SnO(2) NPs. Additionally, we demonstrate that inhibition of ion transport is not due to the dissolution of ZnO NPs and subsequent interactions of zinc ions with lysenin channels. CONCLUSION: We conclude that electrostatic interactions between positively charged ZnO NPs and negative charges within the lysenin channels are responsible for the inhibitory effects on the transport of ions. These interactions point to a potential mechanism of cytotoxicity, which may not require NP internalization. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12951-017-0327-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-57324042017-12-21 ZnO nanoparticles modulate the ionic transport and voltage regulation of lysenin nanochannels Bryant, Sheenah L. Eixenberger, Josh E. Rossland, Steven Apsley, Holly Hoffmann, Connor Shrestha, Nisha McHugh, Michael Punnoose, Alex Fologea, Daniel J Nanobiotechnology Research BACKGROUND: The insufficient understanding of unintended biological impacts from nanomaterials (NMs) represents a serious impediment to their use for scientific, technological, and medical applications. While previous studies have focused on understanding nanotoxicity effects mostly resulting from cellular internalization, recent work indicates that NMs may interfere with transmembrane transport mechanisms, hence enabling contributions to nanotoxicity by affecting key biological activities dependent on transmembrane transport. In this line of inquiry, we investigated the effects of charged nanoparticles (NPs) on the transport properties of lysenin, a pore-forming toxin that shares fundamental features with ion channels such as regulation and high transport rate. RESULTS: The macroscopic conductance of lysenin channels greatly diminished in the presence of cationic ZnO NPs. The inhibitory effects were asymmetrical relative to the direction of the electric field and addition site, suggesting electrostatic interactions between ZnO NPs and a binding site. Similar changes in the macroscopic conductance were observed when lysenin channels were reconstituted in neutral lipid membranes, implicating protein-NP interactions as the major contributor to the reduced transport capabilities. In contrast, no inhibitory effects were observed in the presence of anionic SnO(2) NPs. Additionally, we demonstrate that inhibition of ion transport is not due to the dissolution of ZnO NPs and subsequent interactions of zinc ions with lysenin channels. CONCLUSION: We conclude that electrostatic interactions between positively charged ZnO NPs and negative charges within the lysenin channels are responsible for the inhibitory effects on the transport of ions. These interactions point to a potential mechanism of cytotoxicity, which may not require NP internalization. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12951-017-0327-9) contains supplementary material, which is available to authorized users. BioMed Central 2017-12-16 /pmc/articles/PMC5732404/ /pubmed/29246155 http://dx.doi.org/10.1186/s12951-017-0327-9 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Bryant, Sheenah L.
Eixenberger, Josh E.
Rossland, Steven
Apsley, Holly
Hoffmann, Connor
Shrestha, Nisha
McHugh, Michael
Punnoose, Alex
Fologea, Daniel
ZnO nanoparticles modulate the ionic transport and voltage regulation of lysenin nanochannels
title ZnO nanoparticles modulate the ionic transport and voltage regulation of lysenin nanochannels
title_full ZnO nanoparticles modulate the ionic transport and voltage regulation of lysenin nanochannels
title_fullStr ZnO nanoparticles modulate the ionic transport and voltage regulation of lysenin nanochannels
title_full_unstemmed ZnO nanoparticles modulate the ionic transport and voltage regulation of lysenin nanochannels
title_short ZnO nanoparticles modulate the ionic transport and voltage regulation of lysenin nanochannels
title_sort zno nanoparticles modulate the ionic transport and voltage regulation of lysenin nanochannels
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732404/
https://www.ncbi.nlm.nih.gov/pubmed/29246155
http://dx.doi.org/10.1186/s12951-017-0327-9
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