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Article Dans Une Revue Biophysical Journal Année : 2020

Atomic force microscopy imaging and nanomechanical properties of six Tau isoform assemblies

Résumé

The amyloid fibrillar form of the protein Tau is involved in a number of neurodegenerative diseases, also known as tauopathies. In this work, six different fibrillar Tau isoforms were assembled in vitro. The morphological and nanomechanical properties of these isoforms were studied using atomic force microscopy at high resolution in air and buffer. Our results demonstrate that all Tau isoform fibrils exhibit paired-helical-filament-like structures consisting of two protofibrils separated by a shallow groove. Interestingly, whereas the N-terminal inserts do not contribute to any morphological or mechanical difference between the isoforms with the same carboxyl-terminal microtubule-binding domain repeats, isoforms with four microtubule repeats (4R) exhibited a persistence length ranging from 2.0 to 2.8 mm, almost twofold higher than those with three repeats (3R). In addition, the axial Young's modulus values derived from the persistence lengths, as well as their radial ones determined via nanoindentation experiments, were very low compared to amyloid fibrils made of other proteins. This sheds light on the weak intermolecular interaction acting between the paired b-sheets within Tau fibrils. This may play an important role in their association into high molecular weight assemblies, their dynamics, their persistence, their clearance in cells, and their propagation.
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Dates et versions

hal-03035064 , version 1 (14-12-2020)

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Ali Makky, Luc Bousset, Karine Madiona, Ronald Melki. Atomic force microscopy imaging and nanomechanical properties of six Tau isoform assemblies. Biophysical Journal, 2020, 119, pp.2497-2507. ⟨10.1016/j.bpj.2020.10.045⟩. ⟨hal-03035064⟩
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