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Subcellular localization of biomolecules and drug distribution by high-definition ion beam imaging
Simultaneous visualization of the relationship between multiple biomolecules and their ligands or small molecules at the nanometer scale in cells will enable greater understanding of how biological processes operate. We present here high-definition multiplex ion beam imaging (HD-MIBI), a secondary i...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324837/ https://www.ncbi.nlm.nih.gov/pubmed/34330905 http://dx.doi.org/10.1038/s41467-021-24822-1 |
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author | Rovira-Clavé, Xavier Jiang, Sizun Bai, Yunhao Zhu, Bokai Barlow, Graham Bhate, Salil Coskun, Ahmet F. Han, Guojun Ho, Chin-Min Kimmy Hitzman, Chuck Chen, Shih-Yu Bava, Felice-Alessio Nolan, Garry P. |
author_facet | Rovira-Clavé, Xavier Jiang, Sizun Bai, Yunhao Zhu, Bokai Barlow, Graham Bhate, Salil Coskun, Ahmet F. Han, Guojun Ho, Chin-Min Kimmy Hitzman, Chuck Chen, Shih-Yu Bava, Felice-Alessio Nolan, Garry P. |
author_sort | Rovira-Clavé, Xavier |
collection | PubMed |
description | Simultaneous visualization of the relationship between multiple biomolecules and their ligands or small molecules at the nanometer scale in cells will enable greater understanding of how biological processes operate. We present here high-definition multiplex ion beam imaging (HD-MIBI), a secondary ion mass spectrometry approach capable of high-parameter imaging in 3D of targeted biological entities and exogenously added structurally-unmodified small molecules. With this technology, the atomic constituents of the biomolecules themselves can be used in our system as the “tag” and we demonstrate measurements down to ~30 nm lateral resolution. We correlated the subcellular localization of the chemotherapy drug cisplatin simultaneously with five subnuclear structures. Cisplatin was preferentially enriched in nuclear speckles and excluded from closed-chromatin regions, indicative of a role for cisplatin in active regions of chromatin. Unexpectedly, cells surviving multi-drug treatment with cisplatin and the BET inhibitor JQ1 demonstrated near total cisplatin exclusion from the nucleus, suggesting that selective subcellular drug relocalization may modulate resistance to this important chemotherapeutic treatment. Multiplexed high-resolution imaging techniques, such as HD-MIBI, will enable studies of biomolecules and drug distributions in biologically relevant subcellular microenvironments by visualizing the processes themselves in concert, rather than inferring mechanism through surrogate analyses. |
format | Online Article Text |
id | pubmed-8324837 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-83248372021-08-03 Subcellular localization of biomolecules and drug distribution by high-definition ion beam imaging Rovira-Clavé, Xavier Jiang, Sizun Bai, Yunhao Zhu, Bokai Barlow, Graham Bhate, Salil Coskun, Ahmet F. Han, Guojun Ho, Chin-Min Kimmy Hitzman, Chuck Chen, Shih-Yu Bava, Felice-Alessio Nolan, Garry P. Nat Commun Article Simultaneous visualization of the relationship between multiple biomolecules and their ligands or small molecules at the nanometer scale in cells will enable greater understanding of how biological processes operate. We present here high-definition multiplex ion beam imaging (HD-MIBI), a secondary ion mass spectrometry approach capable of high-parameter imaging in 3D of targeted biological entities and exogenously added structurally-unmodified small molecules. With this technology, the atomic constituents of the biomolecules themselves can be used in our system as the “tag” and we demonstrate measurements down to ~30 nm lateral resolution. We correlated the subcellular localization of the chemotherapy drug cisplatin simultaneously with five subnuclear structures. Cisplatin was preferentially enriched in nuclear speckles and excluded from closed-chromatin regions, indicative of a role for cisplatin in active regions of chromatin. Unexpectedly, cells surviving multi-drug treatment with cisplatin and the BET inhibitor JQ1 demonstrated near total cisplatin exclusion from the nucleus, suggesting that selective subcellular drug relocalization may modulate resistance to this important chemotherapeutic treatment. Multiplexed high-resolution imaging techniques, such as HD-MIBI, will enable studies of biomolecules and drug distributions in biologically relevant subcellular microenvironments by visualizing the processes themselves in concert, rather than inferring mechanism through surrogate analyses. Nature Publishing Group UK 2021-07-30 /pmc/articles/PMC8324837/ /pubmed/34330905 http://dx.doi.org/10.1038/s41467-021-24822-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Rovira-Clavé, Xavier Jiang, Sizun Bai, Yunhao Zhu, Bokai Barlow, Graham Bhate, Salil Coskun, Ahmet F. Han, Guojun Ho, Chin-Min Kimmy Hitzman, Chuck Chen, Shih-Yu Bava, Felice-Alessio Nolan, Garry P. Subcellular localization of biomolecules and drug distribution by high-definition ion beam imaging |
title | Subcellular localization of biomolecules and drug distribution by high-definition ion beam imaging |
title_full | Subcellular localization of biomolecules and drug distribution by high-definition ion beam imaging |
title_fullStr | Subcellular localization of biomolecules and drug distribution by high-definition ion beam imaging |
title_full_unstemmed | Subcellular localization of biomolecules and drug distribution by high-definition ion beam imaging |
title_short | Subcellular localization of biomolecules and drug distribution by high-definition ion beam imaging |
title_sort | subcellular localization of biomolecules and drug distribution by high-definition ion beam imaging |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324837/ https://www.ncbi.nlm.nih.gov/pubmed/34330905 http://dx.doi.org/10.1038/s41467-021-24822-1 |
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