The twisted tauopathies: surface interactions of helically patterned filaments seen in alzheimer's disease and elsewhere

Abstract

This paper broadly examines the dynamics of helically patterned filaments interacting with a surface and focuses on the surface interaction of amyloid fibrils formed by tau protein. Two structures are addressed in detail: cylindrical filaments with periodic thinning (CF-PT) and paired helical filaments (PHFs). PHFs are observed in neural tissue affected by Alzheimer’s disease and may aggregate to form the pathological neurofibrillary tangles associated with the illness. Work using electron microscopy has demonstrated the conversion of CF-PT into PHFs in vitro, suggesting CF-PT to be a PHF precursor in vivo. Here we model CF-PT as a patterned elastic rod placed on a flat surface (characteristic of the environment during microscopy) and examine the conformational changes resulting in stable surface bonding. Analysis of this conformational space reveals structures resembling PHFs and thus provides a mechanistic explanation of the CF-PT to PHF transition. We develop a general phase diagram of the filament conformation as a function of filament twist and bend rigidity. Results of this work also suggest that we can obtain desired filament conformations by patterning interactions of elastic filaments with a substrate, and therefore can be used as a method in microfabrication.

Mutual Sliding Motion of Wrapped Filaments for Biomedical and Engineering Applications

“…22 Also, the surface interaction of helical filaments from twisted tauopathies observed in the research of Alzheimer's disease recently attracted significant attention facilitated by the progress in the scanning transmission electron microscopy. 23,24 In addition, the similarity of the cross section of twisting carbon nanotube yarns 25 and the cross section of human muscle fibers also indicates the feasibility of filament twisting during muscle contraction. Some theoretical models of the shape dynamics of helical filaments bound to a surface are available.…”

“…Some theoretical models of the shape dynamics of helical filaments bound to a surface are available. 23,26 In distinction from those works, the model developed here can predict the dynamic configurations of curved filaments in any shape, rather than only an ordinary helix.…”

“…For example, the smooth muscles are found to be twisted and entwine around each other during isotonic contractions . Also, the surface interaction of helical filaments from twisted tauopathies observed in the research of Alzheimer’s disease recently attracted significant attention facilitated by the progress in the scanning transmission electron microscopy. , In addition, the similarity of the cross section of twisting carbon nanotube yarns and the cross section of human muscle fibers also indicates the feasibility of filament twisting during muscle contraction. Some theoretical models of the shape dynamics of helical filaments bound to a surface are available. , In distinction from those works, the model developed here can predict the dynamic configurations of curved filaments in any shape, rather than only an ordinary helix.…”

“…Also, the surface interaction of helical filaments from twisted tauopathies observed in the research of Alzheimer’s disease recently attracted significant attention facilitated by the progress in the scanning transmission electron microscopy. , In addition, the similarity of the cross section of twisting carbon nanotube yarns and the cross section of human muscle fibers also indicates the feasibility of filament twisting during muscle contraction. Some theoretical models of the shape dynamics of helical filaments bound to a surface are available. , In distinction from those works, the model developed here can predict the dynamic configurations of curved filaments in any shape, rather than only an ordinary helix. In addition, the present model accounts for the kinetic friction force acting at the filament–filament interface, which is motivated by the muscle viscosity and the estimate of actin friction coefficient from viscous-like force during muscle contraction, , and the most likely force transition by shear through the endomysium .…”

Stability of the helical configuration of an intrinsically straight semiflexible biopolymer inside a cylindrical cell

“…16 Within the cell, MreB can be either a helix or a ring. [3][4][5][6][7][8][9][10][26][27][28][29][30][31] It was found that MreB filaments have a persistence length 5 to 10 times larger than the bacterial cell size. 3,13 Consequently, the shape of the cell provides a strong constraint on the MreB filament.…”