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A 3D Spheroid Model as a More Physiological System for Cancer-Associated Fibroblasts Differentiation and Invasion In Vitro Studies
Published on: August 8, 2019
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Gap junctions amplify spatial variations in cell volume in proliferating tumor spheroids.
Eoin McEvoy1,2, Yu Long Han3, Ming Guo3
1Center for Engineering Mechanobiology, University of Pennsylvania, Philadelphia, PA, USA.
Nature Communications
|December 2, 2020
Summary
Cancer cells control volume in 3D clusters through a mechano-osmotic model. Mechanical stress and gap junctions drive osmotic pressure gradients, influencing cell swelling and potentially aiding cancer progression.
Area of Science:
- Multicellular systems biology
- Cancer progression mechanisms
- Biophysics of cell volume regulation
Background:
- Sustained cancer cell proliferation drives tumor growth.
- Cell size is linked to cell-cycle progression.
- Mechanisms controlling cell volume in 3D multicellular clusters are not fully understood.
Purpose of the Study:
- To investigate the evolution of volume dynamics in multicellular systems using a mechano-osmotic model.
- To elucidate the interplay of cellular components in regulating cell volume.
- To explore the role of gap junctions in cancer progression.
Main Methods:
- Development of a novel mechano-osmotic model for multicellular systems.
- Simulation of volume dynamics considering gap junctions, mechanosensitive ion channels, ion pumps, and the actomyosin cortex.
- Analysis of the impact of mechanical loading and proliferation-induced solid stress on cellular osmolarity and volume.
Main Results:
- Mechanical loading induces osmotic pressure gradients between connected cells.
- Increased cellular ion concentrations lead to cell swelling.
- Gap junctions amplify spatial variations in cell volume within multicellular spheroids.
- Volume changes are dependent on proliferation-induced solid stress.
Conclusions:
- The mechano-osmotic model provides insights into cell volume control in 3D clusters.
- Gap junctions play a significant role in modulating cell volume heterogeneity.
- Findings may offer new perspectives on the involvement of gap junctions in breast cancer progression.
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