Keratin filament mechanics and energy dissipation are determined by metal-like plasticity.

Cell mechanics are determined by an intracellular biopolymer network, including intermediate filaments that are expressed in a cell-type-specific manner. A prominent pair of intermediate filaments are keratin and vimentin, as they are expressed by non-motile and motile cells, respectively. Therefore, the differential expression of these proteins coincides with a change in cellular mechanics and dynamic properties of the cells. This observation raises the question of how the mechanical properties already differ on the single filament level. Here, we use optical tweezers and a computational model to compare the stretching and dissipation behavior of the two filament types. We find that keratin and vimentin filaments behave in opposite ways: keratin filaments elongate but retain their stiffness, whereas vimentin filaments soften but retain their length. This finding is explained by fundamentally different ways to dissipate energy: viscous sliding of subunits within keratin filaments and non-equilibrium α helix unfolding in vimentin filaments.

Lateral Subunit Coupling Determines Intermediate Filament Mechanics.

The cytoskeleton is a composite network of three types of protein filaments, among which intermediate filaments (IFs) are the most extensible ones. Two very important IFs are keratin and vimentin, which have similar molecular architectures but different mechanical behaviors. Here we compare the mechanical response of single keratin and vimentin filaments using optical tweezers. We show that the mechanics of vimentin strongly depends on the ionic strength of the buffer and that its force-strain curve suggests a high degree of cooperativity between subunits. Indeed, a computational model indicates that in contrast to keratin, vimentin is characterized by strong lateral subunit coupling of its charged monomers during unfolding of α helices. We conclude that cells can tune their mechanics by differential use of keratin versus vimentin.

Vimentin Intermediate Filaments Undergo Irreversible Conformational Changes during Cyclic Loading.

Intermediate filaments (IFs) are part of the cytoskeleton of eukaryotic cells and, therefore, are largely responsible for the cell's 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, α-helices in vimentin IFs might unfold to ß-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 the nanoscale can be fully rescued by introducing cross-linkers that prevent transition to the ß-sheet. Our results classify IFs as a nanomaterial with intriguing mechanical properties, which is likely to play a major role for the cell's local adaption to external stimuli.