PT  - JOURNAL ARTICLE
AU  - Nachiket Vartak
AU  - Georgia Guenther
AU  - Florian Joly
AU  - Amruta Damle-Vartak
AU  - Gudrun Wibbelt
AU  - Jörns Fickel
AU  - Simone Jörs
AU  - Brigitte Begher-Tibbe
AU  - Adrian Friebel
AU  - Kasimir Wansing
AU  - Ahmed Ghallab
AU  - Marie Rosselin
AU  - Noemie Boissier
AU  - Irene Vignon-Clementel
AU  - Christian Hedberg
AU  - Fabian Geisler
AU  - Heribert Hofer
AU  - Peter Jansen
AU  - Stefan Hoehme
AU  - Dirk Drasdo
AU  - Jan G. Hengstler
TI  - Intravital multi-modal flux analysis reveals the transport mechanism of bile acids through hepatic microconduits
AID  - 10.1101/778803
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 778803
4099  - http://biorxiv.org/content/early/2019/09/26/778803.short
4100  - http://biorxiv.org/content/early/2019/09/26/778803.full
AB  - 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.One Sentence Summary Bile flux proceeds by diffusion in canaliculi, augmented by advection in ducts.