A Predictive 3D Multi-Scale Model of Biliary Fluid Dynamics in the Liver Lobule

Abstract:

Bile, the central metabolic product of the liver, is transported by the bile canaliculi network. The impairment of bile flow in cholestatic liver diseases has urged a demand for insights into its regulation. Here, we developed a predictive 3D multi-scale model that simulates fluid dynamic properties successively from the subcellular to the tissue level. The model integrates the structure of the bile canalicular network in the mouse liver lobule, as determined by high-resolution confocal and serial block-face scanning electron microscopy, with measurements of bile transport by intravital microscopy. The combined experiment-theory approach revealed spatial heterogeneities of biliary geometry and hepatocyte transport activity. Based on this, our model predicts gradients of bile velocity and pressure in the liver lobule. Validation of the model predictions by pharmacological inhibition of Rho kinase demonstrated a requirement of canaliculi contractility for bile flow in vivo. Our model can be applied to functionally characterize liver diseases and quantitatively estimate biliary transport upon drug-induced liver injury.

SEEK ID: https://seek.lisym.org/publications/44

DOI: 10.1016/j.cels.2017.02.008

Projects: LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)

Publication type: Not specified

Journal: Cell Systems

Citation: Cell Systems 4(3) : 277

Date Published: 1st Mar 2017

Registered Mode: Not specified

Authors: Kirstin Meyer, Oleksandr Ostrenko, Georgios Bourantas, Hernan Morales-Navarrete, Natalie Porat-Shliom, Fabian Segovia-Miranda, Hidenori Nonaka, Ali Ghaemi, Jean-Marc Verbavatz, Lutz Brusch, Ivo Sbalzarini, Yannis Kalaidzidis, Roberto Weigert, Marino Zerial

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Meyer, K., Ostrenko, O., Bourantas, G., Morales-Navarrete, H., Porat-Shliom, N., Segovia-Miranda, F., Nonaka, H., Ghaemi, A., Verbavatz, J.-M., Brusch, L., Sbalzarini, I., Kalaidzidis, Y., Weigert, R., & Zerial, M. (2017). A Predictive 3D Multi-Scale Model of Biliary Fluid Dynamics in the Liver Lobule. In Cell Systems (Vol. 4, Issue 3, pp. 277–290.e9). Elsevier BV. https://doi.org/10.1016/j.cels.2017.02.008
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Created: 19th Dec 2017 at 15:12

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