dc.contributor.author
Eckstein, Johannes
dc.contributor.author
Berndt, Nikolaus
dc.contributor.author
Holzhütter, Hermann-Georg
dc.date.accessioned
2018-06-08T03:17:40Z
dc.date.available
2015-05-11T10:53:49.883Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/14869
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-19058
dc.description.abstract
The bile fluid contains various lipids that are secreted at the canalicular
membrane of hepatocytes. As the secretion mechanism is still a matter of
debate and a direct experimental observation of the secretion process is not
possible so far, we used a mathematical model to simulate the extraction of
the major bile lipids cholesterol, phosphatidylcholine and sphingomyelin from
the outer leaflet of the canalicular membrane. Lipid diffusion was modeled as
random movement on a triangular lattice governed by next-neighbor interaction
energies. Phase separation in liquid-ordered and liquid-disordered domains was
modeled by assigning two alternative ordering states to each lipid species and
minimization of next-neighbor ordering energies. Parameterization of the model
was performed such that experimentally determined diffusion rates and phases
in ternary lipid mixtures of model membranes were correctly recapitulated. The
model describes the spontaneous formation of nanodomains in the external
leaflet of the canalicular membrane in a time window between 0.1 ms to 10 ms
at varying lipid proportions. The extraction of lipid patches from the bile
salt soluble nanodomain into the bile reproduced observed biliary phospholipid
compositions for a physiologi-cal membrane composition. Comparing the outcome
of model simulations with available experi-mental observations clearly favors
the extraction of tiny membrane patches composed of about 100–400 lipids as
the likely mechanism of biliary lipid secretion.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie
dc.title
Computer Simulations Suggest a Key Role of Membranous Nanodomains in Biliary
Lipid Secretion
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
PLoS Comput Biol. - 11 (2015), 2, Artikel Nr. e1004033
dcterms.bibliographicCitation.doi
10.1371/journal.pcbi.1004033
dcterms.bibliographicCitation.url
http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004033
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000022399
refubium.note.author
Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000004891
dcterms.accessRights.openaire
open access