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King J, Giselbrecht S, Truckenmüller R, et al. Mechanistic Computational Models of Epithelial Cell Transporters-the Adorned Heroes of Pharmacokinetics. Front Pharmacol. 2021;12:780620doi: 10.3389/fphar.2021.780620.
King, J., Giselbrecht, S., Truckenmüller, R., & Carlier, A. (2021). Mechanistic Computational Models of Epithelial Cell Transporters-the Adorned Heroes of Pharmacokinetics. Frontiers in pharmacology, 12780620. https://doi.org/10.3389/fphar.2021.780620
King, Jasia, et al. "Mechanistic Computational Models of Epithelial Cell Transporters-the Adorned Heroes of Pharmacokinetics." Frontiers in pharmacology vol. 12 (2021): 780620. doi: https://doi.org/10.3389/fphar.2021.780620
King J, Giselbrecht S, Truckenmüller R, Carlier A. Mechanistic Computational Models of Epithelial Cell Transporters-the Adorned Heroes of Pharmacokinetics. Front Pharmacol. 2021 Nov 04;12:780620. doi: 10.3389/fphar.2021.780620. eCollection 2021. PMID: 34803720; PMCID: PMC8599978.
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Front Pharmacol. 2021 Nov 04;12:780620. doi: 10.3389/fphar.2021.780620. eCollection 2021.

Mechanistic Computational Models of Epithelial Cell Transporters-the Adorned Heroes of Pharmacokinetics.

Frontiers in pharmacology

Jasia King, Stefan Giselbrecht, Roman Truckenmüller, Aurélie Carlier

Affiliations

  1. Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands.
  2. Department of Instructive Biomaterials Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands.

PMID: 34803720 PMCID: PMC8599978 DOI: 10.3389/fphar.2021.780620

Abstract

Epithelial membrane transporter kinetics portray an irrefutable role in solute transport in and out of cells. Mechanistic models are used to investigate the transport of solutes at the organ, tissue, cell or membrane scale. Here, we review the recent advancements in using computational models to investigate epithelial transport kinetics on the cell membrane. Various methods have been employed to develop transport phenomena models of solute flux across the epithelial cell membrane. Interestingly, we noted that many models used lumped parameters, such as the Michaelis-Menten kinetics, to simplify the transporter-mediated reaction term. Unfortunately, this assumption neglects transporter numbers or the fact that transport across the membrane may be affected by external cues. In contrast, more recent mechanistic transporter kinetics models account for the transporter number. By creating models closer to reality researchers can investigate the downstream effects of physical or chemical disturbances on the system. Evidently, there is a need to increase the complexity of mechanistic models investigating the solute flux across a membrane to gain more knowledge of transporter-solute interactions by assigning individual parameter values to the transporter kinetics and capturing their dependence on each other. This change results in better pharmacokinetic predictions in larger scale platforms. More reliable and efficient model predictions can be made by creating mechanistic computational models coupled with dedicated

Copyright © 2021 King, Giselbrecht, Truckenmüller and Carlier.

Keywords: computational mechanistic models; epithelial membrane; lumped parameter; pharmacokinetics; transporter

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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