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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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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. |
format | Online Article Text |
id | pubmed-5732404 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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