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Cell mass and cell cycle dynamics of an asynchronous budding yeast population: Experimental observations, flow cytometry data analysis, and multi-scale modeling

Fernandes, Rita Lencastre ; Carlquist, Magnus LU ; Lundin, Luisa ; Heins, Anna-Lena ; Dutta, Abhishek ; Sorensen, Soren J. ; Jensen, Anker D. ; Nopens, Ingmar ; Lantz, Anna Eliasson and Gernaey, Krist V. (2013) In Biotechnology and Bioengineering 110(3). p.812-826
Abstract
Despite traditionally regarded as identical, cells in a microbial cultivation present a distribution of phenotypic traits, forming a heterogeneous cell population. Moreover, the degree of heterogeneity is notably enhanced by changes in micro-environmental conditions. A major development in experimental single-cell studies has taken place in the last decades. It has however not been fully accompanied by similar contributions within data analysis and mathematical modeling. Indeed, literature reporting, for example, quantitative analyses of experimental single-cell observations and validation of model predictions for cell property distributions against experimental data is scarce. This study focuses on the experimental and mathematical... (More)
Despite traditionally regarded as identical, cells in a microbial cultivation present a distribution of phenotypic traits, forming a heterogeneous cell population. Moreover, the degree of heterogeneity is notably enhanced by changes in micro-environmental conditions. A major development in experimental single-cell studies has taken place in the last decades. It has however not been fully accompanied by similar contributions within data analysis and mathematical modeling. Indeed, literature reporting, for example, quantitative analyses of experimental single-cell observations and validation of model predictions for cell property distributions against experimental data is scarce. This study focuses on the experimental and mathematical description of the dynamics of cell size and cell cycle position distributions, of a population of Saccharomyces cerevisiae, in response to the substrate consumption observed during batch cultivation. The good agreement between the proposed multi-scale model (a population balance model [PBM] coupled to an unstructured model) and experimental data (both the overall physiology and cell size and cell cycle distributions) indicates that a mechanistic model is a suitable tool for describing the microbial population dynamics in a bioreactor. This study therefore contributes towards the understanding of the development of heterogeneous populations during microbial cultivations. More generally, it consists of a step towards a paradigm change in the study and description of cell cultivations, where average cell behaviors observed experimentally now are interpreted as a potential joint result of various co-existing single-cell behaviors, rather than a unique response common to all cells in the cultivation. Biotechnol. Bioeng. 2013; 110: 812826. (c) 2012 Wiley Periodicals, Inc. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
population balance model (PBM), multiscale modeling, flow cytometry, standardized data analysis, Saccharomyces cerevisiae, total protein, content, cell cycle
in
Biotechnology and Bioengineering
volume
110
issue
3
pages
812 - 826
publisher
John Wiley & Sons Inc.
external identifiers
  • wos:000313806400015
  • scopus:84872673703
  • pmid:23055296
ISSN
1097-0290
DOI
10.1002/bit.24749
language
English
LU publication?
yes
id
354d05b0-57d8-4a58-bdc4-62788cdf3d2b (old id 3577156)
date added to LUP
2016-04-01 10:06:43
date last changed
2022-02-02 06:28:35
@article{354d05b0-57d8-4a58-bdc4-62788cdf3d2b,
  abstract     = {{Despite traditionally regarded as identical, cells in a microbial cultivation present a distribution of phenotypic traits, forming a heterogeneous cell population. Moreover, the degree of heterogeneity is notably enhanced by changes in micro-environmental conditions. A major development in experimental single-cell studies has taken place in the last decades. It has however not been fully accompanied by similar contributions within data analysis and mathematical modeling. Indeed, literature reporting, for example, quantitative analyses of experimental single-cell observations and validation of model predictions for cell property distributions against experimental data is scarce. This study focuses on the experimental and mathematical description of the dynamics of cell size and cell cycle position distributions, of a population of Saccharomyces cerevisiae, in response to the substrate consumption observed during batch cultivation. The good agreement between the proposed multi-scale model (a population balance model [PBM] coupled to an unstructured model) and experimental data (both the overall physiology and cell size and cell cycle distributions) indicates that a mechanistic model is a suitable tool for describing the microbial population dynamics in a bioreactor. This study therefore contributes towards the understanding of the development of heterogeneous populations during microbial cultivations. More generally, it consists of a step towards a paradigm change in the study and description of cell cultivations, where average cell behaviors observed experimentally now are interpreted as a potential joint result of various co-existing single-cell behaviors, rather than a unique response common to all cells in the cultivation. Biotechnol. Bioeng. 2013; 110: 812826. (c) 2012 Wiley Periodicals, Inc.}},
  author       = {{Fernandes, Rita Lencastre and Carlquist, Magnus and Lundin, Luisa and Heins, Anna-Lena and Dutta, Abhishek and Sorensen, Soren J. and Jensen, Anker D. and Nopens, Ingmar and Lantz, Anna Eliasson and Gernaey, Krist V.}},
  issn         = {{1097-0290}},
  keywords     = {{population balance model (PBM); multiscale modeling; flow cytometry; standardized data analysis; Saccharomyces cerevisiae; total protein; content; cell cycle}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{812--826}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Biotechnology and Bioengineering}},
  title        = {{Cell mass and cell cycle dynamics of an asynchronous budding yeast population: Experimental observations, flow cytometry data analysis, and multi-scale modeling}},
  url          = {{http://dx.doi.org/10.1002/bit.24749}},
  doi          = {{10.1002/bit.24749}},
  volume       = {{110}},
  year         = {{2013}},
}