Viscoelastic properties of vimentin originate from nonequilibrium conformational changes

Block, Johanna; Witt, Hannes; Candelli, Andrea; Danés, Jordi Cabanas; Peterman, Erwin J.G.; Wuite, Gijs J. L.; Janshoff, Andreas; Köster, Sarah

doi:10.1126/sciadv.aat1161

Cited by 63 publications

(210 citation statements)

References 45 publications

Supporting

Mentioning

190

Contrasting

Order By: Relevance

“…This roughness of the energy landscape might indeed give rise to the viscoelastic relaxation behavior investigated earlier, where we find a power law behavior. 13 When the random coil is elongated, hydrogen bonding between parallel polypeptide chains can lead to the formation of β-sheets (red arrow).…”

Section: Figurementioning

confidence: 99%

“…As a consequence, IFs stand out among the cytoskeletal filaments by their high flexibility 8,9 and enormous extensibility. [10][11][12][13] Within the IF family, vimentin is typical for cells of mesenchymal origin. 14 Like all cytoskeletal IFs, vimentin monomers comprise an α-helical rod domain with intrinsically unstructured head and tail domains.…”

mentioning

confidence: 99%

“…S5). e Simulation of force-strain curves according to Block et al 13 without any back-reaction but with a decreasing persistence length for the retraction part of the curves. f Simulation of force-strain curves according to Block et al 13 with back-reaction for different ∆G.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Vimentin intermediate filaments undergo irreversible conformational changes during cyclic loading

Forsting

Kraxner

Witt

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Intermediate filaments (IFs) are part of the cytoskeleton of eukaryotic cells and are thus 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 β-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 β-sheet. Our results classify IFs as a nano-1 material with intriguing mechanical properties, which is likely to play a major role for the cell's local adaption to external stimuli.Keywords: cell mechanics, cytoskeleton, intermediate filaments, force-strain behavior, 3-state system, optical tweezers.The mechanical properties of biological cells are defined by the cytoskeleton, a composite network of microtubules, actin filaments and intermediate filaments (IF). 1,2 Although the exact division of labour among the three filament types is still not fully resolved, 1,2 there is ample evidence that IFs are the load bearing elements when cells are subjected to external tensile 3,4 or compressive 5 stress. During embryogenesis and tissue formation, in particular, cells undergo dramatic changes in shape and size. The force scales expected for cellular processes lie between single motor protein forces of a few pN, which can be measured by FRET sensors, 6 and the collective forces of several nN measured for whole cells, as determined, e.g., by traction force microscopy. 7 In order to withstand strong transitions, cells show reversible superelasticity, which is linked to their IF network. 3 In order to achieve the required material properties for IFs, nature applies design principles on the nanoscale distinct from human engineering solutions and instead relies on self-organization and structural hierarchy. As a consequence, IFs stand out among the cytoskeletal filaments by their high flexibility 8,9 and enormous extensibility. [10][11][12][13] Within the IF family, vimentin is typical for cells of mesenchymal origin. 14 Like all cytoskeletal IFs, vimentin monomers comprise an α-helical rod domain with intrinsically unstructured head and tail domains. 15 The monomers assemble following a hierarchical pathway resulting in filaments with laterally and longitudinally arranged monomers ( Fig. 1a). 16,17 Theoretical considerations, 12,13 molecular dynamics simulations 18,19 and Xray diffraction studies 20 have shown that the intriguing tensile properties of IFs originate from conformational changes on different levels of the hierarchical filament structure. no. 654148). Further financial support was received from the Deutsche Forsch...

show abstract

Section: Figurementioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Vimentin intermediate filaments undergo irreversible conformational changes during cyclic loading

Forsting

Kraxner

Witt

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…This indicates that no viscous structural element contributed to filament mechanics ( Supplementary Fig. 10) suggesting that the energy is stored in the sheet structure 55 . Interestingly, we observed a direct correlation between the force a filament was able to tolerate before its apparent failure and the stiffness, implying that as a filament stiffened, its capacity to bear load also increased ( Supplementary Fig.…”

Section: H Supplementarymentioning

confidence: 99%

“…An engineering strain of ≈126% (Supplementary Note 1) before stiffening is observed, similar to other semi-flexible filaments whose persistence and contour lengths are of similar magnitude 4,53 . Unfolding of -helical coiled-coils before transition into -sheet is a well-known phenomenon 54 , and has been suggested for vimentin 55 , fibrin and fibrinogen during blood clotting 43,56 .…”

Section: Detailed Mechanical Behaviour Of Lamin Filamentsmentioning

confidence: 99%

Nonlinear mechanics of lamin filaments and the meshwork topology build an emergent nuclear lamina

Sapra

Qin

Dubrovsky-Gaupp

et al. 2019

Preprint

View full text Add to dashboard Cite

The nuclear laminaa meshwork of intermediate filaments termed laminsfunctions as a mechanotransduction interface between the extracellular matrix and the nucleus via the cytoskeleton. Although lamins are primarily responsible for the mechanical stability of the nucleus in multicellular organisms, in situ characterization of lamin filaments under tension has remained elusive. Here, we apply an integrative approach combining atomic force microscopy, cryoelectron tomography, network analysis, and molecular dynamics simulations to directly measure the mechanical response of single lamin filaments in its threedimensional meshwork. Endogenous lamin filaments portray non-Hookean behaviorthey deform reversibly under a force of a few hundred picoNewtons and stiffen at nanoNewton forces. The filaments are extensible, strong and tough, similar to natural silk and superior to the synthetic polymer Kevlar ® . Graph theory analysis shows that the lamin meshwork is not a random arrangement of filaments but the meshwork topology follows 'small world' properties. Our results suggest that the lamin filaments arrange to form a robust, emergent meshwork that dictates the mechanical properties of individual lamin filaments. The combined approach provides quantitative insights into the structure-function organization of lamins in situ, and implies a role of meshwork topology in laminopathies.

show abstract

Viscoelastic Cell Microenvironment: Hydrogel‐Based Strategy for Recapitulating Dynamic ECM Mechanics

Han

Yang

et al. 2021

Adv Funct Materials

113

121

View full text Add to dashboard Cite

The native extracellular matrix (ECM) generally exhibits dynamic mechanical properties and displays time‐dependent responses to deformation or mechanical loading, in terms of viscoelastic behaviors (e.g., stress relaxation and creep). Viscoelasticity of the ECM plays a critical role in development, homeostasis, and tissue regeneration, and its implication in disease progression has also been recognized recently. Hydrogels with tunable viscoelastic properties hold a great promise to recapitulate such time‐dependent mechanics found in native ECM, which have been recently used to regulate cell behavior and guide cell fate. Here the importance of tissue viscoelasticity is first highlighted, the molecular mechanisms of hydrogel viscoelasticity are summarized, and characterization techniques used at the macroscale and microscale are reviewed. Then, recent advances in developing novel hydrogels with tunable viscoelasticity through varying crosslinking strategies, engineering of viscoelastic cell microenvironment and its substantial effects on cell behavior and fate are described, and the underlying mechanobiology mechanisms are subsequently discussed. Finally, the ongoing challenges and future perspectives on the design and modulation of viscoelastic hydrogels and the mechanobiology mechanisms on cellular responses to viscoelastic cell microenvironment are proposed.

show abstract

Viscoelastic properties of vimentin originate from nonequilibrium conformational changes

Abstract: Hierarchical molecular architecture renders intracellular vimentin a high-performance, shock-absorbing material.

Cited by 63 publications

References 45 publications

Vimentin intermediate filaments undergo irreversible conformational changes during cyclic loading

Vimentin intermediate filaments undergo irreversible conformational changes during cyclic loading

Nonlinear mechanics of lamin filaments and the meshwork topology build an emergent nuclear lamina

Viscoelastic Cell Microenvironment: Hydrogel‐Based Strategy for Recapitulating Dynamic ECM Mechanics

Contact Info

Product

Resources

About