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Intravital dynamic and correlative imaging reveals diffusion-dominated canalicular and flow-augmented ductular bile flux

Abstract (Expand)

Small-molecule flux in tissue-microdomains is essential for organ function, but knowledge of this process is scant due to the lack of suitable methods applicable to live animals. We developed a methodology … based on dynamic and correlative imaging for quantitative intravital flux analysis. Application to the liver, challenged the prevailing ‘mechano-osmotic’ theory of canalicular bile flow. After active transport across hepatocyte membranes bile salts are transported in the canaliculi primarily by diffusion. Only in the interlobular ducts, diffusion is augmented by regulatable advection. We corroborate these observations with in silico simulations and pan-species comparisons of lobule size. This study demonstrates a flux mechanism, where the energy invested in transmembrane transport entropically dissipates in a sub-micron scale vessel network.

Authors: Nachiket Vartak, Georgia Guenther, Florian Joly, Amruta Damle-Vartak, Gudrun Wibbelt, Jörns Fickel, Simone Jörs, Brigitte Begher-Tibbe, Adrian Friebel, Kasimir Wansing, Ahmed Ghallab, Marie Rosselin, Noemie Boissier, Irene Vignon-Clementel, Christian Hedberg, Fabian Geisler, Heribert Hofer, Peter Jansen, Stefan Hoehme, Dirk Drasdo, Jan G. Hengstler

Date Published: 26th Sep 2019

Publication Type: Journal

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