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@ARTICLE{Fichou:279712,
author = {Fichou, Yann and Schirò, Giorgio and Gallat,
François-Xavier and Laguri, Cedric and Moulin, Martine and
Combet, Jérôme and Zamponi, Michaela and Härtlein,
Michael and Picart, Catherine and Mossou, Estelle and
Lortat-Jacob, Hugues and Colletier, Jacques-Philippe and
Tobias, Douglas J. and Weik, Martin},
title = {{H}ydration water mobility is enhanced around tau amyloid
fibers},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {112},
number = {20},
issn = {1091-6490},
address = {Washington, DC},
publisher = {National Acad. of Sciences},
reportid = {FZJ-2015-07594},
pages = {6365 - 6370},
year = {2015},
abstract = {The paired helical filaments (PHF) formed by the
intrinsically disordered human protein tau are one of the
pathological hallmarks of Alzheimer disease. PHF are fibers
of amyloid nature that are composed of a rigid core and an
unstructured fuzzy coat. The mechanisms of fiber formation,
in particular the role that hydration water might play,
remain poorly understood. We combined protein deuteration,
neutron scattering, and all-atom molecular dynamics
simulations to study the dynamics of hydration water at the
surface of fibers formed by the full-length human protein
htau40. In comparison with monomeric tau, hydration water on
the surface of tau fibers is more mobile, as evidenced by an
increased fraction of translationally diffusing water
molecules, a higher diffusion coefficient, and increased
mean-squared displacements in neutron scattering
experiments. Fibers formed by the hexapeptide 306VQIVYK311
were taken as a model for the tau fiber core and studied by
molecular dynamics simulations, revealing that hydration
water dynamics around the core domain is significantly
reduced after fiber formation. Thus, an increase in water
dynamics around the fuzzy coat is proposed to be at the
origin of the experimentally observed increase in hydration
water dynamics around the entire tau fiber. The observed
increase in hydration water dynamics is suggested to promote
fiber formation through entropic effects. Detection of the
enhanced hydration water mobility around tau fibers is
conjectured to potentially contribute to the early diagnosis
of Alzheimer patients by diffusion MRI.},
cin = {JCNS (München) ; Jülich Centre for Neutron Science JCNS
(München) ; JCNS-FRM-II / Neutronenstreuung ; JCNS-1},
ddc = {000},
cid = {I:(DE-Juel1)JCNS-FRM-II-20110218 /
I:(DE-Juel1)JCNS-1-20110106},
pnm = {6G15 - FRM II / MLZ (POF3-6G15) / 6G4 - Jülich Centre for
Neutron Research (JCNS) (POF3-623)},
pid = {G:(DE-HGF)POF3-6G15 / G:(DE-HGF)POF3-6G4},
experiment = {EXP:(DE-MLZ)SPHERES-20140101},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000354729500052},
pubmed = {pmid:25918405},
doi = {10.1073/pnas.1422824112},
url = {https://juser.fz-juelich.de/record/279712},
}