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@ARTICLE{Huisman:837998,
author = {Huisman, Brooke and Hoore, Masoud and Gompper, Gerhard and
Fedosov, Dmitry A.},
title = {{M}odeling the cleavage of von {W}illebrand factor by
{ADAMTS}13 protease in shear flow},
journal = {Medical engineering $\&$ physics},
volume = {48},
issn = {1350-4533},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {FZJ-2017-06746},
pages = {14 - 22},
year = {2017},
abstract = {Von Willebrand factor (VWF) is a key protein in hemostasis
as it mediates adhesion of blood platelets to a site of
vascular injury. A proper distribution of VWF lengths is
important for normal functioning of hemostatic processes,
because a diminished number of long VWF chains may
significantly limit blood clotting and lead to bleeding,
while an abundant number of long VWFs may result in
undesired thrombotic events. VWF size distribution is
controlled by ADAMTS13 protease, which can cleave VWF chains
beyond a critical shear rate when the chains are stretched
enough such that cleavage sites become accessible. To better
understand the cleavage process, we model VWF cleavage in
shear flow using mesoscopic hydrodynamic simulations. Two
cleavage models are proposed, a geometrical model based on
the degree of local stretching of VWF, and a tension-force
model based on instantaneous tension force within VWF bonds.
Both models capture the susceptibility of VWF to cleavage at
high shear rates; however, the geometrical model appears to
be much more robust than the force model. Our simulations
show that VWF susceptibility to cleavage in shear flow
becomes a universal function of shear rate, independent of
VWF length for long enough chains. Furthermore, VWF is
cleaved with a higher probability close to its ends in
comparison to cleaving in the middle, which results into
longer circulation lifetimes of VWF multimers. Simulations
of dynamic cleavage of VWF show an exponential distribution
of chain lengths, consistently with available in vitro
experiments. The proposed cleavage models can be used in
realistic simulations of hemostatic processes in blood
flow.},
cin = {ICS-2 / JARA-HPC},
ddc = {610},
cid = {I:(DE-Juel1)ICS-2-20110106 / $I:(DE-82)080012_20140620$},
pnm = {553 - Physical Basis of Diseases (POF3-553) / Margination
and Adhesion of Particles and Cells in Blood Flow
$(jiff44_20140501)$ / Blood Flow Resistance in Microvascular
Networks $(jics21_20131101)$},
pid = {G:(DE-HGF)POF3-553 / $G:(DE-Juel1)jiff44_20140501$ /
$G:(DE-Juel1)jics21_20131101$},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28734872},
UT = {WOS:000413177800003},
doi = {10.1016/j.medengphy.2017.06.044},
url = {https://juser.fz-juelich.de/record/837998},
}