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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

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Authors

Benjamin Allcock

Profile image of Wenbin Wei

Dr Wenbin Wei wenbin.wei2@durham.ac.uk
Chief Experimental Officer (Bioinformatics)

Henry Hoyle h.w.hoyle@durham.ac.uk
PGR Student Doctor of Philosophy

Alisha Robert

Rebecca Quelch-Cliffe

Adam Hayward

Jim Cooper



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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