Biology subjects

Forsting, J.

Publications and source records attributed to Forsting, J..

3 recordsLinked to original sources

bioRxiv2022

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

Cell mechanics is 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 the epithelial-to-mesenchymal transition is associated with a switch from keratin to vimentin. The transition coincides with a change in cellular mechanics, and thus 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 subunits sliding within keratin filaments and non-equilibrium helix unfolding in vimentin filaments.

biophysics↗

bioRxiv2019

Lateral Subunit Coupling Determines Intermediate Filament Mechanics

The cytoskeleton is a composite network of three types of protein filaments, among which in-termediate 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 -helices. We conclude that cells can tune their mechanics by differential use of keratin versus vimentin.

biophysics↗

bioRxiv2019

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 cells 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, -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 the nanoscale can be fully rescued by introducing crosslinkers that prevent transition to the {beta}-sheet. Our results classify IFs as a nano-material with intriguing mechanical properties, which is likely to play a major role for the cells local adaption to external stimuli.

biophysics↗