Post-Translational Modifications Soften Vimentin Intermediate Filaments


Kraxner J, Lorenz C, Menzel J, Parfentev I, Silbern I, Denz M, Urlaub H, Schwappach B, Köster S




Nanoscale. 2020 Dec 22.


The mechanical properties of biological cells are determined by the cytoskeleton, a composite biopolymer network consisting of microtubules, actin filaments and intermediate filaments (IFs). By differential expression of the cytoskeletal proteins, modulation of the network architecture and the interactions between the filaments, cell mechanics may be adapted to varying requirements on the cell. Here, we focus on the intermediate filament protein vimentin and introduce post-translational modifications as an additional, much faster mechanism for mechanical modulation. We study the impact of phosphorylation on filament mechanics by recording precise force-strain curves using optical traps. Whereas full phosphorylation leads to disassembly of IFs, partial phosphorylation results in softening of the filaments. We show that binding of the protein 14–3–3 to phosphorylated vimentin IFs further enhances this effect and speculate that in the cell 14–3–3 may serve to preserve the softening and thereby the altered cell mechanics. By employing phosphomimetic mutants and complementary Monte Carlo simulations, we explain our observation through the additional charges introduced during.


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