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

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 inv...

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Autores principales:	Jasia King, Stefan Giselbrecht, Roman Truckenmüller, Aurélie Carlier
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	transporter computational mechanistic models epithelial membrane lumped parameter pharmacokinetics Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/ca9b7d4ce03c430b9ff60bb5a75b94ea
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spelling	oai:doaj.org-article:ca9b7d4ce03c430b9ff60bb5a75b94ea2021-11-04T06:42:07ZMechanistic Computational Models of Epithelial Cell Transporters-the Adorned Heroes of Pharmacokinetics1663-981210.3389/fphar.2021.780620https://doaj.org/article/ca9b7d4ce03c430b9ff60bb5a75b94ea2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.780620/fullhttps://doaj.org/toc/1663-9812Epithelial 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 in vitro experiments. It is also vital to foster collaborative efforts among transporter kinetics researchers in the modeling, material science and biological fields.Jasia KingJasia KingStefan GiselbrechtRoman TruckenmüllerAurélie CarlierFrontiers Media S.A.articletransportercomputational mechanistic modelsepithelial membranelumped parameterpharmacokineticsTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	transporter computational mechanistic models epithelial membrane lumped parameter pharmacokinetics Therapeutics. Pharmacology RM1-950
spellingShingle	transporter computational mechanistic models epithelial membrane lumped parameter pharmacokinetics Therapeutics. Pharmacology RM1-950 Jasia King Jasia King Stefan Giselbrecht Roman Truckenmüller Aurélie Carlier Mechanistic Computational Models of Epithelial Cell Transporters-the Adorned Heroes of Pharmacokinetics
description	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 in vitro experiments. It is also vital to foster collaborative efforts among transporter kinetics researchers in the modeling, material science and biological fields.
format	article
author	Jasia King Jasia King Stefan Giselbrecht Roman Truckenmüller Aurélie Carlier
author_facet	Jasia King Jasia King Stefan Giselbrecht Roman Truckenmüller Aurélie Carlier
author_sort	Jasia King
title	Mechanistic Computational Models of Epithelial Cell Transporters-the Adorned Heroes of Pharmacokinetics
title_short	Mechanistic Computational Models of Epithelial Cell Transporters-the Adorned Heroes of Pharmacokinetics
title_full	Mechanistic Computational Models of Epithelial Cell Transporters-the Adorned Heroes of Pharmacokinetics
title_fullStr	Mechanistic Computational Models of Epithelial Cell Transporters-the Adorned Heroes of Pharmacokinetics
title_full_unstemmed	Mechanistic Computational Models of Epithelial Cell Transporters-the Adorned Heroes of Pharmacokinetics
title_sort	mechanistic computational models of epithelial cell transporters-the adorned heroes of pharmacokinetics
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/ca9b7d4ce03c430b9ff60bb5a75b94ea
work_keys_str_mv	AT jasiaking mechanisticcomputationalmodelsofepithelialcelltransporterstheadornedheroesofpharmacokinetics AT jasiaking mechanisticcomputationalmodelsofepithelialcelltransporterstheadornedheroesofpharmacokinetics AT stefangiselbrecht mechanisticcomputationalmodelsofepithelialcelltransporterstheadornedheroesofpharmacokinetics AT romantruckenmuller mechanisticcomputationalmodelsofepithelialcelltransporterstheadornedheroesofpharmacokinetics AT aureliecarlier mechanisticcomputationalmodelsofepithelialcelltransporterstheadornedheroesofpharmacokinetics
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Mechanistic Computational Models of Epithelial Cell Transporters-the Adorned Heroes of Pharmacokinetics

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