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Intercellular communication induces glycolytic synchronization waves between individually oscillating cells
Many organs have internal structures with spatially differentiated and sometimes temporally synchronized groups of cells. The mechanisms leading to such differentiation and coordination are not well understood. Here we design a diffusion-limited microfluidic system to mimic a multicellular organ str...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017953/ https://www.ncbi.nlm.nih.gov/pubmed/33526662 http://dx.doi.org/10.1073/pnas.2010075118 |
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author | Mojica-Benavides, Martin van Niekerk, David D. Mijalkov, Mite Snoep, Jacky L. Mehlig, Bernhard Volpe, Giovanni Goksör, Mattias Adiels, Caroline B. |
author_facet | Mojica-Benavides, Martin van Niekerk, David D. Mijalkov, Mite Snoep, Jacky L. Mehlig, Bernhard Volpe, Giovanni Goksör, Mattias Adiels, Caroline B. |
author_sort | Mojica-Benavides, Martin |
collection | PubMed |
description | Many organs have internal structures with spatially differentiated and sometimes temporally synchronized groups of cells. The mechanisms leading to such differentiation and coordination are not well understood. Here we design a diffusion-limited microfluidic system to mimic a multicellular organ structure with peripheral blood flow and test whether a group of individually oscillating yeast cells could form subpopulations of spatially differentiated and temporally synchronized cells. Upon substrate addition, the dynamic response at single-cell level shows glycolytic oscillations, leading to wave fronts traveling through the monolayered population and to synchronized communities at well-defined positions in the cell chamber. A detailed mechanistic model with the architectural structure of the flow chamber incorporated successfully predicts the spatial-temporal experimental data, and allows for a molecular understanding of the observed phenomena. The intricate interplay of intracellular biochemical reaction networks leading to the oscillations, combined with intercellular communication via metabolic intermediates and fluid dynamics of the reaction chamber, is responsible for the generation of the subpopulations of synchronized cells. This mechanism, as analyzed from the model simulations, is experimentally tested using different concentrations of cyanide stress solutions. The results are reproducible and stable, despite cellular heterogeneity, and the spontaneous community development is reminiscent of a zoned cell differentiation often observed in multicellular organs. |
format | Online Article Text |
id | pubmed-8017953 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-80179532021-04-12 Intercellular communication induces glycolytic synchronization waves between individually oscillating cells Mojica-Benavides, Martin van Niekerk, David D. Mijalkov, Mite Snoep, Jacky L. Mehlig, Bernhard Volpe, Giovanni Goksör, Mattias Adiels, Caroline B. Proc Natl Acad Sci U S A Physical Sciences Many organs have internal structures with spatially differentiated and sometimes temporally synchronized groups of cells. The mechanisms leading to such differentiation and coordination are not well understood. Here we design a diffusion-limited microfluidic system to mimic a multicellular organ structure with peripheral blood flow and test whether a group of individually oscillating yeast cells could form subpopulations of spatially differentiated and temporally synchronized cells. Upon substrate addition, the dynamic response at single-cell level shows glycolytic oscillations, leading to wave fronts traveling through the monolayered population and to synchronized communities at well-defined positions in the cell chamber. A detailed mechanistic model with the architectural structure of the flow chamber incorporated successfully predicts the spatial-temporal experimental data, and allows for a molecular understanding of the observed phenomena. The intricate interplay of intracellular biochemical reaction networks leading to the oscillations, combined with intercellular communication via metabolic intermediates and fluid dynamics of the reaction chamber, is responsible for the generation of the subpopulations of synchronized cells. This mechanism, as analyzed from the model simulations, is experimentally tested using different concentrations of cyanide stress solutions. The results are reproducible and stable, despite cellular heterogeneity, and the spontaneous community development is reminiscent of a zoned cell differentiation often observed in multicellular organs. National Academy of Sciences 2021-02-09 2021-02-01 /pmc/articles/PMC8017953/ /pubmed/33526662 http://dx.doi.org/10.1073/pnas.2010075118 Text en Copyright © 2021 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Physical Sciences Mojica-Benavides, Martin van Niekerk, David D. Mijalkov, Mite Snoep, Jacky L. Mehlig, Bernhard Volpe, Giovanni Goksör, Mattias Adiels, Caroline B. Intercellular communication induces glycolytic synchronization waves between individually oscillating cells |
title | Intercellular communication induces glycolytic synchronization waves between individually oscillating cells |
title_full | Intercellular communication induces glycolytic synchronization waves between individually oscillating cells |
title_fullStr | Intercellular communication induces glycolytic synchronization waves between individually oscillating cells |
title_full_unstemmed | Intercellular communication induces glycolytic synchronization waves between individually oscillating cells |
title_short | Intercellular communication induces glycolytic synchronization waves between individually oscillating cells |
title_sort | intercellular communication induces glycolytic synchronization waves between individually oscillating cells |
topic | Physical Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017953/ https://www.ncbi.nlm.nih.gov/pubmed/33526662 http://dx.doi.org/10.1073/pnas.2010075118 |
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