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

Nature communications (2020-12-03)
Eoin McEvoy, Yu Long Han, Ming Guo, Vivek B Shenoy
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Hydrocortisone, BioReagent, suitable for cell culture
Sigma-Aldrich
Cholera Toxin from Vibrio cholerae, ≥90% (SDS-PAGE), lyophilized powder
Sigma-Aldrich
Insulin from bovine pancreas, γ-irradiated, BioXtra, suitable for cell culture, potency: ≥20 units/mg (USP units), lyophilized powder
Sigma-Aldrich
Calcium sulfate, ≥99.99% trace metals basis