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Analysis of the Influence of Cell Heterogeneity on Nanoparticle Dose Response

Matthew J. Ware, Biana Godin, Neenu Singh, Ravish Majithia, Sabeel Shamsudeen, Rita E. Serda, Kenith Meissner, Paul Rees Orcid Logo, Huw Summers Orcid Logo

ACS Nano, Volume: 8, Issue: 7, Pages: 6693 - 6700

Swansea University Authors: Neenu Singh, Kenith Meissner, Paul Rees Orcid Logo, Huw Summers Orcid Logo

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DOI (Published version): 10.1021/nn502356f

Abstract

Understanding the effect of variability in the interaction of individual cells with nanoparticles on the overall response of the cell population to a nanoagent is a fundamental challenge in bionanotechnology. Here, we show that the technique of time-resolved, high-throughput microscopy can be used i...

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Published in: ACS Nano
ISSN: 1936-0851 1936-086X
Published: 2014
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URI: https://cronfa.swan.ac.uk/Record/cronfa20184
first_indexed 2015-02-20T03:00:00Z
last_indexed 2020-09-30T02:33:55Z
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spelling 2020-09-29T12:11:20.7206839 v2 20184 2015-02-19 Analysis of the Influence of Cell Heterogeneity on Nanoparticle Dose Response 25f7165923805db3197691b8e76c97df Neenu Singh Neenu Singh true false 30fdfec0d8b19b59b57a818e054d4af3 Kenith Meissner Kenith Meissner true false 537a2fe031a796a3bde99679ee8c24f5 0000-0002-7715-6914 Paul Rees Paul Rees true false a61c15e220837ebfa52648c143769427 0000-0002-0898-5612 Huw Summers Huw Summers true false 2015-02-19 Understanding the effect of variability in the interaction of individual cells with nanoparticles on the overall response of the cell population to a nanoagent is a fundamental challenge in bionanotechnology. Here, we show that the technique of time-resolved, high-throughput microscopy can be used in this endeavor. Mass measurement with single-cell resolution provides statistically robust assessments of cell heterogeneity, while the addition of a temporal element allows assessment of separate processes leading to deconvolution of the effects of particle supply and biological response. We provide a specific demonstration of the approach, in vitro, through time-resolved measurement of fibroblast cell (HFF-1) death caused by exposure to cationic nanoparticles. The results show that heterogeneity in cell area is the major source of variability with area-dependent nanoparticle capture rates determining the time of cell death and hence the form of the exposure–response characteristic. Moreover, due to the particulate nature of the nanoparticle suspension, there is a reduction in the particle concentration over the course of the experiment, eventually causing saturation in the level of measured biological outcome. A generalized mathematical description of the system is proposed, based on a simple model of particle depletion from a finite supply reservoir. This captures the essential aspects of the nanoparticle–cell interaction dynamics and accurately predicts the population exposure–response curves from individual cell heterogeneity distributions. Journal Article ACS Nano 8 7 6693 6700 1936-0851 1936-086X bionanotechnology; dose−response characteristic; high-throughput microscopy; nanomedicine; nanoparticle dose; nanoparticle exposure; nanotoxicology 22 7 2014 2014-07-22 10.1021/nn502356f ACS AuthorChoice - Terms of Use CC-BY COLLEGE NANME COLLEGE CODE Swansea University 2020-09-29T12:11:20.7206839 2015-02-19T11:25:22.4712205 Faculty of Science and Engineering School of Engineering and Applied Sciences - Biomedical Engineering Matthew J. Ware 1 Biana Godin 2 Neenu Singh 3 Ravish Majithia 4 Sabeel Shamsudeen 5 Rita E. Serda 6 Kenith Meissner 7 Paul Rees 0000-0002-7715-6914 8 Huw Summers 0000-0002-0898-5612 9 0020184-13102016103123.pdf ware2016(2).pdf 2016-10-13T10:31:23.2470000 Output 1683011 application/pdf Version of Record true 2016-10-13T00:00:00.0000000 false
title Analysis of the Influence of Cell Heterogeneity on Nanoparticle Dose Response
spellingShingle Analysis of the Influence of Cell Heterogeneity on Nanoparticle Dose Response
Neenu Singh
Kenith Meissner
Paul Rees
Huw Summers
title_short Analysis of the Influence of Cell Heterogeneity on Nanoparticle Dose Response
title_full Analysis of the Influence of Cell Heterogeneity on Nanoparticle Dose Response
title_fullStr Analysis of the Influence of Cell Heterogeneity on Nanoparticle Dose Response
title_full_unstemmed Analysis of the Influence of Cell Heterogeneity on Nanoparticle Dose Response
title_sort Analysis of the Influence of Cell Heterogeneity on Nanoparticle Dose Response
author_id_str_mv 25f7165923805db3197691b8e76c97df
30fdfec0d8b19b59b57a818e054d4af3
537a2fe031a796a3bde99679ee8c24f5
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author_id_fullname_str_mv 25f7165923805db3197691b8e76c97df_***_Neenu Singh
30fdfec0d8b19b59b57a818e054d4af3_***_Kenith Meissner
537a2fe031a796a3bde99679ee8c24f5_***_Paul Rees
a61c15e220837ebfa52648c143769427_***_Huw Summers
author Neenu Singh
Kenith Meissner
Paul Rees
Huw Summers
author2 Matthew J. Ware
Biana Godin
Neenu Singh
Ravish Majithia
Sabeel Shamsudeen
Rita E. Serda
Kenith Meissner
Paul Rees
Huw Summers
format Journal article
container_title ACS Nano
container_volume 8
container_issue 7
container_start_page 6693
publishDate 2014
institution Swansea University
issn 1936-0851
1936-086X
doi_str_mv 10.1021/nn502356f
college_str Faculty of Science and Engineering
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hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Engineering and Applied Sciences - Biomedical Engineering{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Biomedical Engineering
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description Understanding the effect of variability in the interaction of individual cells with nanoparticles on the overall response of the cell population to a nanoagent is a fundamental challenge in bionanotechnology. Here, we show that the technique of time-resolved, high-throughput microscopy can be used in this endeavor. Mass measurement with single-cell resolution provides statistically robust assessments of cell heterogeneity, while the addition of a temporal element allows assessment of separate processes leading to deconvolution of the effects of particle supply and biological response. We provide a specific demonstration of the approach, in vitro, through time-resolved measurement of fibroblast cell (HFF-1) death caused by exposure to cationic nanoparticles. The results show that heterogeneity in cell area is the major source of variability with area-dependent nanoparticle capture rates determining the time of cell death and hence the form of the exposure–response characteristic. Moreover, due to the particulate nature of the nanoparticle suspension, there is a reduction in the particle concentration over the course of the experiment, eventually causing saturation in the level of measured biological outcome. A generalized mathematical description of the system is proposed, based on a simple model of particle depletion from a finite supply reservoir. This captures the essential aspects of the nanoparticle–cell interaction dynamics and accurately predicts the population exposure–response curves from individual cell heterogeneity distributions.
published_date 2014-07-22T18:38:41Z
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