Gap junctions amplify spatial variations in cell volume in proliferating tumor spheroids
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s41467-020-19904-5.pdf
Description
Published version
Size
1.47 MB
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Unknown
Checksum (MD5)
1d7dd225308886ee4c4bae71a1abfae0
Author(s)
McEvoy, Eoin
Han, Yu Long
Guo, Ming
Shenoy, Vivek B
Date Issued
2020
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
McEvoy, Eoin, Han, Yu Long, Guo, Ming and Shenoy, Vivek B. 2020. "Gap junctions amplify spatial variations in cell volume in proliferating tumor spheroids." Nature Communications, 11 (1).
Version
Final published version
Abstract
© 2020, The Author(s). 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.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/S41467-020-19904-5
