title: The fuzzy coat of pathological human Tau fibrils is a two-layered polyelectrolyte brush.
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.
authors.affiliation: Department of Biosystems Science and Engineering,  Eidgenössiche Technische Hochschule Zürich, 4058 Basel,  Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Wegmann
authors.forename: Izhar D
authors.initials: ID
authors.lastname: Medalsy
authors.forename: Eckhard
authors.initials: E
authors.lastname: Mandelkow
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
mesh_terms: D000268:Adhesiveness; D001696:Biomechanical Phenomena; D004573:Electrolytes / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018625:Microscopy, Atomic Force; D016253:Microscopy, Immunoelectron; D008958:Models, Molecular; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure; D016875:tau Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure*
chemical_list: D004573:Electrolytes; C054369:MAPT protein, human; D011994:Recombinant Proteins; D016875:tau Proteins