Hydration water mobility is enhanced around tau amyloid fibers.
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 (306)VQIVYK(311) 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.
Université Grenoble Alpes, CNRS, and Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut de Biologie Structurale, 38044 Grenoble, France; martin.weik@ibs.fr yann.fichou@ibs.fr dtobias@uci.edu.
Yann
Y
Fichou
Université Grenoble Alpes, CNRS, and Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut de Biologie Structurale, 38044 Grenoble, France;
Giorgio
G
Schirò
Université Grenoble Alpes, CNRS, and Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut de Biologie Structurale, 38044 Grenoble, France;
François-Xavier
FX
Gallat
Université Grenoble Alpes, CNRS, and Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut de Biologie Structurale, 38044 Grenoble, France;
Cedric
C
Laguri
Life Sciences Group, Institut Laue-Langevin, 38000 Grenoble, France;
Martine
M
Moulin
Institut Laue Langevin, 38000 Grenoble, France; Institut Charles Sadron CNRS-UdS, 67034 Strasbourg, France;
Jérôme
J
Combet
Jülich Centre for Neutron Science, outstation at Heinz Maier-Leibnitz Zentrum, Forschungszentrum Jülich GmbH, 85747 Garching, Germany;
Michaela
M
Zamponi
Life Sciences Group, Institut Laue-Langevin, 38000 Grenoble, France;
Michael
M
Härtlein
CNRS, UMR 5628, LMGP, 38016 Grenoble, France; Université de Grenoble Alpes, Grenoble Institute of Technology, 38016 Grenoble, France;
Catherine
C
Picart
Life Sciences Group, Institut Laue-Langevin, 38000 Grenoble, France; Faculty of Natural Sciences, Keele University, Staffordshire ST5 5BG, United Kingdom; and.
Estelle
E
Mossou
Université Grenoble Alpes, CNRS, and Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut de Biologie Structurale, 38044 Grenoble, France;
Hugues
H
Lortat-Jacob
Université Grenoble Alpes, CNRS, and Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut de Biologie Structurale, 38044 Grenoble, France;
Jacques-Philippe
JP
Colletier
Department of Chemistry, University of California, Irvine, CA 92697-2025 martin.weik@ibs.fr yann.fichou@ibs.fr dtobias@uci.edu.
Douglas J
DJ
Tobias
Université Grenoble Alpes, CNRS, and Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut de Biologie Structurale, 38044 Grenoble, France; martin.weik@ibs.fr yann.fichou@ibs.fr dtobias@uci.edu.
Martin
M
Weik
D000544:Alzheimer Disease / Q000175:diagnosis*; D000682:Amyloid / Q000096:biosynthesis / Q000737:chemistry*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008854:Microscopy, Electron; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D066263:Protein Aggregation, Pathological / Q000378:metabolism*; D014867:Water / Q000737:chemistry*; D016875:tau Proteins
D000682:Amyloid; D008565:Membrane Proteins; D014867:Water; C054369:MAPT protein, human; D016875:tau Proteins
amyloid fibers; hydration water; intrinsically disordered proteins; neutron scattering; tau protein