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Gap junctions amplify spatial variations in cell volume in proliferating tumor spheroids

Sustained proliferation is a significant driver of cancer progression. Cell-cycle advancement is coupled with cell size, but it remains unclear how multiple cells interact to control their volume in 3D clusters. In this study, we propose a mechano-osmotic model to investigate the evolution of volume...

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Detalles Bibliográficos
Autores principales: McEvoy, Eoin, Han, Yu Long, Guo, Ming, Shenoy, Vivek B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708487/
https://www.ncbi.nlm.nih.gov/pubmed/33262337
http://dx.doi.org/10.1038/s41467-020-19904-5
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author McEvoy, Eoin
Han, Yu Long
Guo, Ming
Shenoy, Vivek B.
author_facet McEvoy, Eoin
Han, Yu Long
Guo, Ming
Shenoy, Vivek B.
author_sort McEvoy, Eoin
collection PubMed
description Sustained proliferation is a significant driver of cancer progression. Cell-cycle advancement is coupled with cell size, but it remains unclear how multiple cells interact to control their volume in 3D clusters. In this study, we propose a mechano-osmotic model to investigate the evolution of volume dynamics within multicellular systems. Volume control depends on an interplay between multiple cellular constituents, including gap junctions, mechanosensitive ion channels, energy-consuming ion pumps, and the actomyosin cortex, that coordinate to manipulate cellular osmolarity. In connected cells, we show that mechanical loading leads to the emergence of osmotic pressure gradients between cells with consequent increases in cellular ion concentrations driving swelling. We identify how gap junctions can amplify spatial variations in cell volume within multicellular spheroids and, further, describe how the process depends on proliferation-induced solid stress. Our model may provide new insight into the role of gap junctions in breast cancer progression.
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spelling pubmed-77084872020-12-03 Gap junctions amplify spatial variations in cell volume in proliferating tumor spheroids McEvoy, Eoin Han, Yu Long Guo, Ming Shenoy, Vivek B. Nat Commun Article Sustained proliferation is a significant driver of cancer progression. Cell-cycle advancement is coupled with cell size, but it remains unclear how multiple cells interact to control their volume in 3D clusters. In this study, we propose a mechano-osmotic model to investigate the evolution of volume dynamics within multicellular systems. Volume control depends on an interplay between multiple cellular constituents, including gap junctions, mechanosensitive ion channels, energy-consuming ion pumps, and the actomyosin cortex, that coordinate to manipulate cellular osmolarity. In connected cells, we show that mechanical loading leads to the emergence of osmotic pressure gradients between cells with consequent increases in cellular ion concentrations driving swelling. We identify how gap junctions can amplify spatial variations in cell volume within multicellular spheroids and, further, describe how the process depends on proliferation-induced solid stress. Our model may provide new insight into the role of gap junctions in breast cancer progression. Nature Publishing Group UK 2020-12-01 /pmc/articles/PMC7708487/ /pubmed/33262337 http://dx.doi.org/10.1038/s41467-020-19904-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
McEvoy, Eoin
Han, Yu Long
Guo, Ming
Shenoy, Vivek B.
Gap junctions amplify spatial variations in cell volume in proliferating tumor spheroids
title Gap junctions amplify spatial variations in cell volume in proliferating tumor spheroids
title_full Gap junctions amplify spatial variations in cell volume in proliferating tumor spheroids
title_fullStr Gap junctions amplify spatial variations in cell volume in proliferating tumor spheroids
title_full_unstemmed Gap junctions amplify spatial variations in cell volume in proliferating tumor spheroids
title_short Gap junctions amplify spatial variations in cell volume in proliferating tumor spheroids
title_sort gap junctions amplify spatial variations in cell volume in proliferating tumor spheroids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708487/
https://www.ncbi.nlm.nih.gov/pubmed/33262337
http://dx.doi.org/10.1038/s41467-020-19904-5
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