title: How does a single cell know when the liver has reached its correct size?
abstract: The liver is a multi-functional organ that regulates major physiological processes and that possesses a remarkable regeneration capacity. After loss of functional liver mass the liver grows back to its original, individual size through hepatocyte proliferation and apoptosis. How does a single hepatocyte 'know' when the organ has grown to its final size? This work considers the initial growth phase of liver regeneration after partial hepatectomy in which the mass is restored. There are strong and valid arguments that the trigger of proliferation after partial hepatectomy is mediated through the portal blood flow. It remains unclear, if either or both the concentration of metabolites in the blood or the shear stress are crucial to hepatocyte proliferation and liver size control. A cell-based mathematical model is developed that helps discriminate the effects of these two potential triggers. Analysis of the mathematical model shows that a metabolic load and a hemodynamical hypothesis imply different feedback mechanisms at the cellular scale. The predictions of the developed mathematical model are compared to experimental data in rats. The assumption that hepatocytes are able to buffer the metabolic load leads to a robustness against short-term fluctuations of the trigger which can not be achieved with a purely hemodynamical trigger.
authors.affiliation: Center for Information Services and High Performance Computing, Technical University Dresden, Dresden, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Hohmann
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University Hospital Jena, Jena, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Weiwei
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University Hospital Jena, Jena, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Dahmen
authors.affiliation: Institute of Pathology, University Hospital Jena, Jena, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Dirsch
authors.affiliation: Center for Information Services and High Performance Computing, Technical University Dresden, Dresden, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Deutsch
authors.affiliation: Center for Information Services and High Performance Computing, Technical University Dresden, Dresden, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Voss-Böhme
mesh_terms: D000465:Algorithms; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D003198:Computer Simulation; D025461:Feedback, Physiological; D006498:Hepatectomy; D022781:Hepatocytes / Q000502:physiology*; D008099:Liver / Q000033:anatomy & histology* / Q000502:physiology*; D008115:Liver Regeneration / Q000502:physiology*; D023421:Models, Animal; D008962:Models, Theoretical; D009929:Organ Size; D051381:Rats