Benjamin Allcock
Impact of the Physical Cellular Microenvironment on the Structure and Function of a Model Hepatocyte Cell Line for Drug Toxicity Applications
Allcock, Benjamin; Wei, Wenbin; Goncalves, Kirsty; Hoyle, Henry; Robert, Alisha; Quelch-Cliffe, Rebecca; Hayward, Adam; Cooper, Jim; Przyborski, Stefan
Authors
Dr Wenbin Wei wenbin.wei2@durham.ac.uk
Chief Experimental Officer (Bioinformatics)
Kirsty Goncalves kirsty.e.goncalves@durham.ac.uk
Post Doctoral Research Associate
Henry Hoyle h.w.hoyle@durham.ac.uk
PGR Student Doctor of Philosophy
Alisha Robert
Rebecca Quelch-Cliffe
Adam Hayward
Jim Cooper
Professor Stefan Przyborski stefan.przyborski@durham.ac.uk
Deputy Provost
Abstract
It is widely recognised that cells respond to their microenvironment, which has implications for cell culture practices. Growth cues provided by 2D cell culture substrates are far removed from native 3D tissue structure in vivo. Geometry is one of many factors that differs between in vitro culture and in vivo cellular environments. Cultured cells are far removed from their native counterparts and lose some of their predictive capability and reliability. In this study, we examine the cellular processes that occur when a cell is cultured on 2D or 3D surfaces for a short period of 8 days prior to its use in functional assays, which we term: "priming". We follow the process of mechanotransduction from cytoskeletal alterations, to changes to nuclear structure, leading to alterations in gene expression, protein expression and improved functional capabilities. In this study, we utilise HepG2 cells as a hepatocyte model cell line, due to their robustness for drug toxicity screening. Here, we demonstrate enhanced functionality and improved drug toxicity profiles that better reflect the in vivo clinical response. However, findings more broadly reflect in vitro cell culture practises across many areas of cell biology, demonstrating the fundamental impact of mechanotransduction in bioengineering and cell biology.
Citation
Allcock, B., Wei, W., Goncalves, K., Hoyle, H., Robert, A., Quelch-Cliffe, R., …Przyborski, S. (2023). Impact of the Physical Cellular Microenvironment on the Structure and Function of a Model Hepatocyte Cell Line for Drug Toxicity Applications. Cells, 12(19), Article 2408. https://doi.org/10.3390/cells12192408
Journal Article Type | Article |
---|---|
Acceptance Date | Oct 5, 2023 |
Online Publication Date | Oct 5, 2023 |
Publication Date | Oct 1, 2023 |
Deposit Date | Oct 16, 2023 |
Publicly Available Date | Oct 16, 2023 |
Journal | Cells |
Publisher | MDPI |
Peer Reviewed | Peer Reviewed |
Volume | 12 |
Issue | 19 |
Article Number | 2408 |
DOI | https://doi.org/10.3390/cells12192408 |
Keywords | 3D cell culture, hepatocyte, cytotoxicity, mechanotransduction, cytoskeleton, bioengineering, functionality, microenvironment |
Public URL | https://durham-repository.worktribe.com/output/1803762 |
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Copyright Statement
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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