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A mechanobiological mathematical model of liver metabolism

Nikmaneshi, M. R ; Sharif University of Technology | 2020

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  1. Type of Document: Article
  2. DOI: 10.1002/bit.27451
  3. Publisher: John Wiley and Sons Inc , 2020
  4. Abstract:
  5. The liver plays a complex role in metabolism and detoxification, and better tools are needed to understand its function and to develop liver-targeted therapies. In this study, we establish a mechanobiological model of liver transport and hepatocyte biology to elucidate the metabolism of urea and albumin, the production/detoxification of ammonia, and consumption of oxygen and nutrients. Since hepatocellular shear stress (SS) can influence the enzymatic activities of liver, the effect of SS on the urea and albumin synthesis are empirically modeled through the mechanotransduction mechanisms. The results demonstrate that the rheology and dynamics of the sinusoid flow can significantly affect liver metabolism. We show that perfusate rheology and blood hematocrit can affect urea and albumin production by changing hepatocyte mechanosensitive metabolism. The model can also simulate enzymatic diseases of the liver such as hyperammonemia I, hyperammonemia II, hyperarginemia, citrollinemia, and argininosuccinicaciduria, which disrupt the urea metabolism and ammonia detoxification. The model is also able to predict how aggregate cultures of hepatocytes differ from single cell cultures. We conclude that in vitro perfusable devices for the study of liver metabolism or personalized medicine should be designed with similar morphology and fluid dynamics as patient liver tissue. This robust model can be adapted to any type of hepatocyte culture to determine how hepatocyte viability, functionality, and metabolism are influenced by liver pathologies and environmental conditions. © 2020 Wiley Periodicals LLC
  6. Keywords:
  7. Hep-G2 ; Cell culture ; Elasticity ; Medicine ; Nutrients ; Shear flow ; Aggregate culture ; Environmental conditions ; Enzymatic activities ; Hepatocyte culture ; Liver metabolisms ; Mechano-transduction mechanism ; Robust modeling ; Single cell cultures ; Metabolism ; Albumin ; Ammonia ; Oxygen ; Urea ; Ammonia formation ; Cell metabolism ; Detoxification ; Enzyme activity ; Flow kinetics ; Fluid flow ; Hematocrit ; Hep-G2 cell line ; Human ; Human cell ; Liver cell ; Liver cell culture ; Liver function ; Liver metabolism ; Liver sinusoid ; Mathematical model ; Mechanotransduction ; Oxygen consumption ; Protein metabolism ; Shear stress ; Simulation ; Urea cycle
  8. Source: Biotechnology and Bioengineering ; Volume 117, Issue 9 , 5 June , 2020 , Pages 2861-2874
  9. URL: https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.27451