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Amyloid single-cell cytotoxicity assays by nanomotion detection
Cells are extremely complex systems able to actively modify their metabolism and behavior in response to environmental conditions and stimuli such as pathogenic agents or drugs. The comprehension of these responses is central to understand the molecular bases of human pathologies, including amyloid...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564330/ https://www.ncbi.nlm.nih.gov/pubmed/28845298 http://dx.doi.org/10.1038/cddiscovery.2017.53 |
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author | Ruggeri, Francesco S Mahul-Mellier, Anne-Laure Kasas, Sandor Lashuel, Hilal A Longo, Giovanni Dietler, Giovanni |
author_facet | Ruggeri, Francesco S Mahul-Mellier, Anne-Laure Kasas, Sandor Lashuel, Hilal A Longo, Giovanni Dietler, Giovanni |
author_sort | Ruggeri, Francesco S |
collection | PubMed |
description | Cells are extremely complex systems able to actively modify their metabolism and behavior in response to environmental conditions and stimuli such as pathogenic agents or drugs. The comprehension of these responses is central to understand the molecular bases of human pathologies, including amyloid misfolding diseases. Conventional bulk biological assays are limited by intrinsic cellular heterogeneity in gene, protein and metabolite expression, and can investigate only indirectly cellular reactions in non-physiological conditions. Here we employ a label-free nanomotion sensor to study single neuroblastoma cells exposed to extracellular monomeric and amyloid α-synuclein species in real-time and in physiological conditions. Combining this technique with fluorescence microscopy, we demonstrate multispecies cooperative cytotoxic effect of amyloids and aggregate-induced loss of cellular membrane integrity. Notably, the method can study cellular reactions and cytotoxicity an order of magnitude faster, and using 100-fold smaller volume of reagents when compared to conventional bulk analyses. This rapidity and sensitivity will allow testing novel pharmacological approaches to stop or delay a wide range of human diseases. |
format | Online Article Text |
id | pubmed-5564330 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-55643302017-08-25 Amyloid single-cell cytotoxicity assays by nanomotion detection Ruggeri, Francesco S Mahul-Mellier, Anne-Laure Kasas, Sandor Lashuel, Hilal A Longo, Giovanni Dietler, Giovanni Cell Death Discov Article Cells are extremely complex systems able to actively modify their metabolism and behavior in response to environmental conditions and stimuli such as pathogenic agents or drugs. The comprehension of these responses is central to understand the molecular bases of human pathologies, including amyloid misfolding diseases. Conventional bulk biological assays are limited by intrinsic cellular heterogeneity in gene, protein and metabolite expression, and can investigate only indirectly cellular reactions in non-physiological conditions. Here we employ a label-free nanomotion sensor to study single neuroblastoma cells exposed to extracellular monomeric and amyloid α-synuclein species in real-time and in physiological conditions. Combining this technique with fluorescence microscopy, we demonstrate multispecies cooperative cytotoxic effect of amyloids and aggregate-induced loss of cellular membrane integrity. Notably, the method can study cellular reactions and cytotoxicity an order of magnitude faster, and using 100-fold smaller volume of reagents when compared to conventional bulk analyses. This rapidity and sensitivity will allow testing novel pharmacological approaches to stop or delay a wide range of human diseases. Nature Publishing Group 2017-08-21 /pmc/articles/PMC5564330/ /pubmed/28845298 http://dx.doi.org/10.1038/cddiscovery.2017.53 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Ruggeri, Francesco S Mahul-Mellier, Anne-Laure Kasas, Sandor Lashuel, Hilal A Longo, Giovanni Dietler, Giovanni Amyloid single-cell cytotoxicity assays by nanomotion detection |
title | Amyloid single-cell cytotoxicity assays by nanomotion detection |
title_full | Amyloid single-cell cytotoxicity assays by nanomotion detection |
title_fullStr | Amyloid single-cell cytotoxicity assays by nanomotion detection |
title_full_unstemmed | Amyloid single-cell cytotoxicity assays by nanomotion detection |
title_short | Amyloid single-cell cytotoxicity assays by nanomotion detection |
title_sort | amyloid single-cell cytotoxicity assays by nanomotion detection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564330/ https://www.ncbi.nlm.nih.gov/pubmed/28845298 http://dx.doi.org/10.1038/cddiscovery.2017.53 |
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