Intercellular communication induces glycolytic synchronization waves between individually oscillating cells.

Autor:	Mojica-Benavides M; Department of Physics, University of Gothenburg, SE-41296 Gothenburg, Sweden., van Niekerk DD; Department of Biochemistry, Stellenbosch University, Matieland 7602, South Africa., Mijalkov M; Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, SE-17177 Stockholm, Sweden., Snoep JL; Department of Biochemistry, Stellenbosch University, Matieland 7602, South Africa.; Molecular Cell Physiology, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands., Mehlig B; Department of Physics, University of Gothenburg, SE-41296 Gothenburg, Sweden., Volpe G; Department of Physics, University of Gothenburg, SE-41296 Gothenburg, Sweden., Goksör M; Department of Physics, University of Gothenburg, SE-41296 Gothenburg, Sweden., Adiels CB; Department of Physics, University of Gothenburg, SE-41296 Gothenburg, Sweden; caroline.adiels@physics.gu.se.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Feb 09; Vol. 118 (6).
DOI:	10.1073/pnas.2010075118
Abstrakt:	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. Competing Interests: The authors declare no competing interest. (Copyright © 2021 the Author(s). Published by PNAS.)
Databáze:	MEDLINE
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