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Journal Articles Physical Review X Year : 2023

Fragmentation and Entanglement Limit Vimentin Intermediate Filament Assembly


Networks of intermediate filaments (IFs) need to constantly reorganize to fulfil their functions at different locations within the cell. The mechanism of IF assembly is well described and involves filament end-to-end annealing. By contrast, the mechanisms involved in IF disassembly are far less understood. In vitro, IFs are assumed to be very stable and their disassembly negligible. IF fragmentation has been observed in many cell types, but it has been suggested to be associated with active processes such as IF post-translational modifications. In this article, we uncover the contribution of filament spontaneous fragmentation in the assembly dynamics of type III vimentin IF using a combination of in vitro reconstitution probed by fluorescence imaging and theoretical modeling. We first show that vimentin assembly at low concentrations results in an equilibrium between filament annealing and fragmentation at times ≥24 h. At higher concentrations, entanglements kinetically trap the system out of equilibrium, and we show that this trapping is reversible upon dilution. Taking into account both fragmentation and entanglement, we estimate that the mean bond breaking time is ∼18 h. This translates into a mean breaking time of ∼5 h for a 1-μm-long filament, which is a relevant timescale for IF reorganization in live cells. Finally, we provide direct evidence through dual-color imaging that filament fragmentation and annealing coexist during assembly. By showing that IF fragmentation can occur without cofactors or posttranslational modifications, our study provides new insights into the physical understanding of the IF length regulation.
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hal-04091040 , version 1 (07-05-2023)





Quang D Tran, Valerio Sorichetti, Gerard Pehau-Arnaudet, Martin Lenz, Cécile Leduc. Fragmentation and Entanglement Limit Vimentin Intermediate Filament Assembly. Physical Review X, 2023, 13 (1), pp.011014. ⟨10.1103/PhysRevX.13.011014⟩. ⟨hal-04091040⟩
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