In silico models for dynamic connected cell cultures mimicking hepatocyte-endothelial cell-adipocyte interaction circle.

The biochemistry of a system made up of three kinds of cell is virtually impossible to work out without the use of in silico models. Here, we deal with homeostatic balance phenomena from a metabolic point of view and we present a new computational model merging three single-cell models, already avai...

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Main Authors: Chiara Andreoni, Gianni Orsi, Carmelo De Maria, Francesca Montemurro, Giovanni Vozzi
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4266517?pdf=render
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spelling doaj-ee73277da8e5466facdf9b7e93f466522020-11-24T21:51:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11194610.1371/journal.pone.0111946In silico models for dynamic connected cell cultures mimicking hepatocyte-endothelial cell-adipocyte interaction circle.Chiara AndreoniGianni OrsiCarmelo De MariaFrancesca MontemurroGiovanni VozziThe biochemistry of a system made up of three kinds of cell is virtually impossible to work out without the use of in silico models. Here, we deal with homeostatic balance phenomena from a metabolic point of view and we present a new computational model merging three single-cell models, already available from our research group: the first model reproduced the metabolic behaviour of a hepatocyte, the second one represented an endothelial cell, and the third one described an adipocyte. Multiple interconnections were created among these three models in order to mimic the main physiological interactions that are known for the examined cell phenotypes. The ultimate aim was to recreate the accomplishment of the homeostatic balance as it was observed for an in vitro connected three-culture system concerning glucose and lipid metabolism in the presence of the medium flow. The whole model was based on a modular approach and on a set of nonlinear differential equations implemented in Simulink, applying Michaelis-Menten kinetic laws and some energy balance considerations to the studied metabolic pathways. Our in silico model was then validated against experimental datasets coming from literature about the cited in vitro model. The agreement between simulated and experimental results was good and the behaviour of the connected culture system was reproduced through an adequate parameter evaluation. The developed model may help other researchers to investigate further about integrated metabolism and the regulation mechanisms underlying the physiological homeostasis.http://europepmc.org/articles/PMC4266517?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Chiara Andreoni
Gianni Orsi
Carmelo De Maria
Francesca Montemurro
Giovanni Vozzi
spellingShingle Chiara Andreoni
Gianni Orsi
Carmelo De Maria
Francesca Montemurro
Giovanni Vozzi
In silico models for dynamic connected cell cultures mimicking hepatocyte-endothelial cell-adipocyte interaction circle.
PLoS ONE
author_facet Chiara Andreoni
Gianni Orsi
Carmelo De Maria
Francesca Montemurro
Giovanni Vozzi
author_sort Chiara Andreoni
title In silico models for dynamic connected cell cultures mimicking hepatocyte-endothelial cell-adipocyte interaction circle.
title_short In silico models for dynamic connected cell cultures mimicking hepatocyte-endothelial cell-adipocyte interaction circle.
title_full In silico models for dynamic connected cell cultures mimicking hepatocyte-endothelial cell-adipocyte interaction circle.
title_fullStr In silico models for dynamic connected cell cultures mimicking hepatocyte-endothelial cell-adipocyte interaction circle.
title_full_unstemmed In silico models for dynamic connected cell cultures mimicking hepatocyte-endothelial cell-adipocyte interaction circle.
title_sort in silico models for dynamic connected cell cultures mimicking hepatocyte-endothelial cell-adipocyte interaction circle.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2014-01-01
description The biochemistry of a system made up of three kinds of cell is virtually impossible to work out without the use of in silico models. Here, we deal with homeostatic balance phenomena from a metabolic point of view and we present a new computational model merging three single-cell models, already available from our research group: the first model reproduced the metabolic behaviour of a hepatocyte, the second one represented an endothelial cell, and the third one described an adipocyte. Multiple interconnections were created among these three models in order to mimic the main physiological interactions that are known for the examined cell phenotypes. The ultimate aim was to recreate the accomplishment of the homeostatic balance as it was observed for an in vitro connected three-culture system concerning glucose and lipid metabolism in the presence of the medium flow. The whole model was based on a modular approach and on a set of nonlinear differential equations implemented in Simulink, applying Michaelis-Menten kinetic laws and some energy balance considerations to the studied metabolic pathways. Our in silico model was then validated against experimental datasets coming from literature about the cited in vitro model. The agreement between simulated and experimental results was good and the behaviour of the connected culture system was reproduced through an adequate parameter evaluation. The developed model may help other researchers to investigate further about integrated metabolism and the regulation mechanisms underlying the physiological homeostasis.
url http://europepmc.org/articles/PMC4266517?pdf=render
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