Vimentin intermediate filaments undergo irreversible conformational changes during cyclic loading

Intermediate filaments (IFs) are part of the cytoskeleton of eukaryotic cells and are thus largely responsible for the cell9s mechanical properties. IFs are characterized by a pronounced extensibility and remarkable resilience that enable them to support cells in extreme situations. Previous experiments showed that under strain, alpha-helices in vimentin IFs might unfold to beta-sheets. Upon repeated stretching, the filaments soften, however, the remaining plastic strain is negligible. Here we observe that vimentin IFs do not recover their original stiffness on reasonable time scales, and we explain these seemingly contradicting results by introducing a third, less well-defined conformational state. Reversibility on a microscopic scale can be fully rescued by introducing crosslinkers that prevent transition to the beta-sheet. Our results classify IFs as a material with intriguing mechanical properties, which is likely to play a major role for the cell9s local adaption to external stimuli.