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Research Article

The fuzzy coat of pathological human Tau fibrils is a two-layered polyelectrolyte brush

Susanne Wegmann, Izhar D. Medalsy, Eckhard Mandelkow, and Daniel J. Müller
  1. aDepartment of Biosystems Science and Engineering, Eidgenössiche Technische Hochschule Zürich, 4058 Basel, Switzerland;
  2. bDepartment of Neurology, Harvard Medical School and Alzheimer’s Disease Research Laboratory, Massachusetts General Hospital, Charlestown, MA 02129;
  3. cGerman Center for Neurodegenerative Diseases, 53175 Bonn, Germany;
  4. dCenter of Advanced European Studies and Research, 53175 Bonn, Germany; and
  5. eMax Planck Institute for Neurological Research Cologne, Hamburg Outstation, 22607 Hamburg, Germany

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PNAS January 22, 2013 110 (4) E313-E321; https://doi.org/10.1073/pnas.1212100110
Susanne Wegmann
aDepartment of Biosystems Science and Engineering, Eidgenössiche Technische Hochschule Zürich, 4058 Basel, Switzerland;
bDepartment of Neurology, Harvard Medical School and Alzheimer’s Disease Research Laboratory, Massachusetts General Hospital, Charlestown, MA 02129;
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  • For correspondence: daniel.mueller@bsse.ethz.ch susanne.wegmann@partners.org
Izhar D. Medalsy
aDepartment of Biosystems Science and Engineering, Eidgenössiche Technische Hochschule Zürich, 4058 Basel, Switzerland;
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Eckhard Mandelkow
cGerman Center for Neurodegenerative Diseases, 53175 Bonn, Germany;
dCenter of Advanced European Studies and Research, 53175 Bonn, Germany; and
eMax Planck Institute for Neurological Research Cologne, Hamburg Outstation, 22607 Hamburg, Germany
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Daniel J. Müller
aDepartment of Biosystems Science and Engineering, Eidgenössiche Technische Hochschule Zürich, 4058 Basel, Switzerland;
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  • For correspondence: daniel.mueller@bsse.ethz.ch susanne.wegmann@partners.org
  1. Edited by Ueli Aebi, University of Basel, Basel, Switzerland, and accepted by the Editorial Board November 21, 2012 (received for review July 18, 2012)

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Abstract

The structure and properties of amyloid-like Tau fibrils accumulating in neurodegenerative diseases have been debated for decades. Although the core of Tau fibrils assembles from short β-strands, the properties of the much longer unstructured Tau domains protruding from the fibril core remain largely obscure. Applying immunogold transmission EM, and force-volume atomic force microscopy (AFM), we imaged human Tau fibrils at high resolution and simultaneously mapped their mechanical and adhesive properties. Tau fibrils showed a ≈16-nm–thick fuzzy coat that resembles a two-layered polyelectrolyte brush, which is formed by the unstructured short C-terminal and long N-terminal Tau domains. The mechanical and adhesive properties of the fuzzy coat are modulated by electrolytes and pH, and thus by the cellular environment. These unique properties of the fuzzy coat help in understanding how Tau fibrils disturb cellular interactions and accumulate in neurofibrillary tangles.

  • protein aggregation
  • Alzheimer’s disease
  • paired helical filaments

Footnotes

  • ↵1To whom correspondence may be addressed. E-mail: daniel.mueller{at}bsse.ethz.ch or susanne.wegmann{at}partners.org.
  • Author contributions: S.W. and D.J.M. designed research; S.W. and I.D.M. performed research; E.M. contributed new reagents/analytic tools; S.W., I.D.M., E.M., and D.J.M. analyzed data; and S.W., I.D.M., E.M., and D.J.M. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission. U.A. is a guest editor invited by the Editorial Board.

  • See Author Summary on page 1156 (volume 110, number 4).

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1212100110/-/DCSupplemental.

Freely available online through the PNAS open access option.

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Quantifying the fuzzy coat of human Tau fibrils
Susanne Wegmann, Izhar D. Medalsy, Eckhard Mandelkow, Daniel J. Müller
Proceedings of the National Academy of Sciences Jan 2013, 110 (4) E313-E321; DOI: 10.1073/pnas.1212100110

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Quantifying the fuzzy coat of human Tau fibrils
Susanne Wegmann, Izhar D. Medalsy, Eckhard Mandelkow, Daniel J. Müller
Proceedings of the National Academy of Sciences Jan 2013, 110 (4) E313-E321; DOI: 10.1073/pnas.1212100110
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Proceedings of the National Academy of Sciences: 110 (4)
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