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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...

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Autores principales: Mojica-Benavides, Martin, van Niekerk, David D., Mijalkov, Mite, Snoep, Jacky L., Mehlig, Bernhard, Volpe, Giovanni, Goksör, Mattias, Adiels, Caroline B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2021
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.
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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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