TY  - JOUR
AU  - Wegmann, Susanne
AU  - Medalsy, Izhar D
AU  - Mandelkow, Eckhard
AU  - Müller, Daniel J
TI  - The fuzzy coat of pathological human Tau fibrils is a two-layered polyelectrolyte brush.
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 110
IS  - 4
SN  - 0027-8424
CY  - Washington, DC
PB  - National Acad. of Sciences
M1  - DZNE-2020-03102
SP  - E313-E321
PY  - 2013
AB  - 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.
KW  - Adhesiveness
KW  - Biomechanical Phenomena
KW  - Electrolytes: chemistry
KW  - Humans
KW  - Hydrogen-Ion Concentration
KW  - Microscopy, Atomic Force
KW  - Microscopy, Immunoelectron
KW  - Models, Molecular
KW  - Protein Interaction Domains and Motifs
KW  - Protein Multimerization
KW  - Recombinant Proteins: chemistry
KW  - Recombinant Proteins: genetics
KW  - Recombinant Proteins: ultrastructure
KW  - tau Proteins: chemistry
KW  - tau Proteins: genetics
KW  - tau Proteins: physiology
KW  - tau Proteins: ultrastructure
KW  - Electrolytes (NLM Chemicals)
KW  - MAPT protein, human (NLM Chemicals)
KW  - Recombinant Proteins (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:23269837
C2  - pmc:PMC3557036
DO  - DOI:10.1073/pnas.1212100110
UR  - https://pub.dzne.de/record/136780
ER  -