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Using stochastic cell division and death to probe minimal units of cellular replication
The invariant cell initiation mass measured in bacterial growth experiments has been interpreted as a minimal unit of cellular replication. Here we argue that the existence of such minimal units induces a coupling between the rates of stochastic cell division and death. To probe this coupling we tra...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOP Publishing
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380804/ https://www.ncbi.nlm.nih.gov/pubmed/30867637 http://dx.doi.org/10.1088/1367-2630/aab197 |
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author | Chib, Savita Das, Suman Venkatesan, Soumya Seshasayee, Aswin Sai Narain Thattai, Mukund |
author_facet | Chib, Savita Das, Suman Venkatesan, Soumya Seshasayee, Aswin Sai Narain Thattai, Mukund |
author_sort | Chib, Savita |
collection | PubMed |
description | The invariant cell initiation mass measured in bacterial growth experiments has been interpreted as a minimal unit of cellular replication. Here we argue that the existence of such minimal units induces a coupling between the rates of stochastic cell division and death. To probe this coupling we tracked live and dead cells in Escherichia coli populations treated with a ribosome-targeting antibiotic. We find that the growth exponent from macroscopic cell growth or decay measurements can be represented as the difference of microscopic first-order cell division and death rates. The boundary between cell growth and decay, at which the number of live cells remains constant over time, occurs at the minimal inhibitory concentration (MIC) of the antibiotic. This state appears macroscopically static but is microscopically dynamic: division and death rates exactly cancel at MIC but each is remarkably high, reaching 60% of the antibiotic-free division rate. A stochastic model of cells as collections of minimal replicating units we term ‘widgets’ reproduces both steady-state and transient features of our experiments. Sub-cellular fluctuations of widget numbers stochastically drive each new daughter cell to one of two alternate fates, division or death. First-order division or death rates emerge as eigenvalues of a stationary Markov process, and can be expressed in terms of the widget’s molecular properties. High division and death rates at MIC arise due to low mean and high relative fluctuations of widget number. Isolating cells at the threshold of irreversible death might allow molecular characterization of this minimal replication unit. |
format | Online Article Text |
id | pubmed-6380804 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | IOP Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-63808042019-03-11 Using stochastic cell division and death to probe minimal units of cellular replication Chib, Savita Das, Suman Venkatesan, Soumya Seshasayee, Aswin Sai Narain Thattai, Mukund New J Phys Paper The invariant cell initiation mass measured in bacterial growth experiments has been interpreted as a minimal unit of cellular replication. Here we argue that the existence of such minimal units induces a coupling between the rates of stochastic cell division and death. To probe this coupling we tracked live and dead cells in Escherichia coli populations treated with a ribosome-targeting antibiotic. We find that the growth exponent from macroscopic cell growth or decay measurements can be represented as the difference of microscopic first-order cell division and death rates. The boundary between cell growth and decay, at which the number of live cells remains constant over time, occurs at the minimal inhibitory concentration (MIC) of the antibiotic. This state appears macroscopically static but is microscopically dynamic: division and death rates exactly cancel at MIC but each is remarkably high, reaching 60% of the antibiotic-free division rate. A stochastic model of cells as collections of minimal replicating units we term ‘widgets’ reproduces both steady-state and transient features of our experiments. Sub-cellular fluctuations of widget numbers stochastically drive each new daughter cell to one of two alternate fates, division or death. First-order division or death rates emerge as eigenvalues of a stationary Markov process, and can be expressed in terms of the widget’s molecular properties. High division and death rates at MIC arise due to low mean and high relative fluctuations of widget number. Isolating cells at the threshold of irreversible death might allow molecular characterization of this minimal replication unit. IOP Publishing 2018-03 2018-03-29 /pmc/articles/PMC6380804/ /pubmed/30867637 http://dx.doi.org/10.1088/1367-2630/aab197 Text en © 2018 The Author(s). Published by IOP Publishing Ltd on behalf of Deutsche Physikalische Gesellschaft http://creativecommons.org/licenses/by/3.0/ Original content from this work may be used under the terms of the Creative Commons Attribution 3.0 licence (http://creativecommons.org/licenses/by/3.0) . Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI. |
spellingShingle | Paper Chib, Savita Das, Suman Venkatesan, Soumya Seshasayee, Aswin Sai Narain Thattai, Mukund Using stochastic cell division and death to probe minimal units of cellular replication |
title | Using stochastic cell division and death to probe minimal units of cellular replication |
title_full | Using stochastic cell division and death to probe minimal units of cellular replication |
title_fullStr | Using stochastic cell division and death to probe minimal units of cellular replication |
title_full_unstemmed | Using stochastic cell division and death to probe minimal units of cellular replication |
title_short | Using stochastic cell division and death to probe minimal units of cellular replication |
title_sort | using stochastic cell division and death to probe minimal units of cellular replication |
topic | Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380804/ https://www.ncbi.nlm.nih.gov/pubmed/30867637 http://dx.doi.org/10.1088/1367-2630/aab197 |
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