Intermediate filaments (IF) are involved in key cellular functions including polarization, migration, and protection against large deformations. These functions are related to their remarkable ability to extend without breaking, a capacity that should be determined by the molecular organization of subunits within filaments. However, this structure-mechanics relationship remains poorly understood at the molecular level. I will present how, using super-resolution microscopy (SRM), we showed that vimentin filaments exhibit a ~49 nm axial repeat both in cells and in vitro. Using a SRM compatible stretching device, we also provided evidence that the extensibility of vimentin is due to the unfolding of its subunits and not to their sliding, thus establishing a direct link between the structural organization and its mechanical properties [1]. In a second part, I will show recent results on the in vitro reconstitution of vimentin assembly dynamics. We showed that vimentin filaments can spontaneously break without cofactors or post-translational modifications, but this fragmentation limits assembly only at very long-time scale (>18h) [2]. We also uncovered the mechanism responsible for fragmentation which involves subunit exchange. Our results show how vimentin filaments self-repair to protect their integrity and provide new insights into the physical understanding of the intermediate filament length regulation.

REFERENCES
[1] F. Nunes Vincente, M. Lelek, J.-Y. Tinevez, Q.D. Tran, G. Pehau-Arnaudet, C. Zimmer, S. Etienne-Manneville, G. Giannone, and C. Leduc, Molecular organization and mechanics of single vimentin filaments revealed by super-resolution imaging, Science Advances 8 (2022) eabm2696. doi: 10.1126/sciadv.abm2696.
[2] Q.D. Tran, V. Sorichetti, G. Pehau-Arnaudet, M. Lenz M+, and C. Leduc, Fragmentation and entanglement limit vimentin intermediate filament assembly, PRX 13 (2023) 011014 doi:10.1103/PhysRevX.13.011014.