Keratins determine network stress responsiveness in reconstituted actin–keratin filament systems

Elbalasy, Iman; Mollenkopf, Paul; Tutmarc, Cary; Herrmann, Harald; Schnauß, Jörg

doi:10.1039/d0sm02261f

Cited by 24 publications

(61 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This agrees with the observed increase in stickiness since the rubber behavior is caused by the transition from an entangled to a crosslinked network. [ 28–30 ] Our findings also illustrate that the increased resistance is not simply caused by the inherently higher solvent viscosity of D 2 O compared to H 2 O [ 10,11 ] since this would not result in a more pronounced rubber‐like behavior. In fact, viscous contributions of the in vitro systems are hardly affected by different H 2 O/D 2 O ratios (see Figure S3, Supporting Information).…”

Section: Discussionmentioning

confidence: 66%

“…In this respect, it is known that deuterium bonds of D 2 O are slightly stronger than the hydrogen bonds of H 2 O [10] and that D 2 O may enhance hydrophobic interactions. [26] Within the glassy worm-like chain model, [27][28][29][30] these interactions are modeled as a stickiness parameter (ε), and a higher ε reflects stronger inter-filament interactions. We found that the stickiness parameter increases under D 2 O conditions non-monotonically from ε = 1.8 for normal H 2 O conditions to 4.6 and 2.7 for the respective D 2 O concentrations (see Supporting Information; since multiple factors can impact the viscoelastic behavior of actin networks, we speculate that the non-monotonic behavior of ε could be caused by a D 2 O induced shortening of filaments).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Cells in Slow Motion: Apparent Undercooling Increases Glassy Behavior at Physiological Temperatures

et al. 2021

Self Cite

View full text Add to dashboard Cite

Solvent conditions are unexpectedly sufficient to drastically and reversibly slow down cells. In vitro on the molecular level, protein–solvent interactions drastically change in the presence of heavy water (D2O) and its stronger hydrogen bonds. Adding D2O to the cell medium of living cells increases the molecular intracellular viscosity. While cell morphology and phenotype remain unchanged, cellular dynamics transform into slow motion in a changeable manner. This is exemplified in the slowdown of cell proliferation and migration, which is caused by a reversible gelation of the cytoplasm. In analogy to the time–temperature superposition principle, where temperature is replaced by D2O, an increase in viscosity slows down the effective time. Actin networks, crucial structures in the cytoplasm, switch from a power‐law‐like viscoelastic to a more rubber‐like elastic behavior. The resulting intracellular resistance and dissipation impair cell movement. Since cells are highly adaptive non‐equilibrium systems, they usually respond irreversibly from a thermodynamic perspective. D2O induced changes, however, are fully reversible and their effects are independent of signaling as well as expression. The stronger hydrogen bonds lead to glass‐like, drawn‐out intramolecular dynamics, which may facilitate longer storage times of biological matter, for instance, during transport of organ transplants.

show abstract

Section: Discussionmentioning

confidence: 66%

Section: Resultsmentioning

confidence: 99%

Cells in Slow Motion: Apparent Undercooling Increases Glassy Behavior at Physiological Temperatures

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…With keratins, the impact of actin is different. Actin causes a steric hindrance, which reduces the bundling of keratin IFs [111,112]. Bulk shear rheology shows that, at low strain, the viscoelastic behavior of actin and K8/18 composite networks reconstituted in vitro is intermediate between that of pure networks.…”

Section: Intermediate Filaments Affect the Mechanics Of Cytoskeletal Composite Networkmentioning

confidence: 99%

“…Bulk shear rheology shows that, at low strain, the viscoelastic behavior of actin and K8/18 composite networks reconstituted in vitro is intermediate between that of pure networks. When submitted to large deformations, the addition of K8/18 increases the strain-stiffening properties and the yield stress [112]. Compared to vimentin, keratin is more efficient in increasing composite network strainstiffening [110,112].…”

Section: Intermediate Filaments Affect the Mechanics Of Cytoskeletal Composite Networkmentioning

confidence: 99%

See 1 more Smart Citation

Intermediate Filaments from Tissue Integrity to Single Molecule Mechanics

Bodegraven

Etienne-Manneville

2021

Cells

View full text Add to dashboard Cite

Cytoplasmic intermediate filaments (IFs), which together with actin and microtubules form the cytoskeleton, are composed of a large and diverse family of proteins. Efforts to elucidate the molecular mechanisms responsible for IF-associated diseases increasingly point towards a major contribution of IFs to the cell’s ability to adapt, resist and respond to mechanical challenges. From these observations, which echo the impressive resilience of IFs in vitro, we here discuss the role of IFs as master integrators of cell and tissue mechanics. In this review, we summarize our current understanding of the contribution of IFs to cell and tissue mechanics and explain these results in light of recent in vitro studies that have investigated physical properties of single IFs and IF networks. Finally, we highlight how changes in IF gene expression, network assembly dynamics, and post-translational modifications can tune IF properties to adapt cell and tissue mechanics to changing environments.

show abstract

Impact of Viscosity on Human Hepatoma Spheroids in Soft Core–Shell Microcapsules

Peng,

Janićijević,

Lemm

et al. 2024

Adv Healthcare Materials

View full text Add to dashboard Cite

The extracellular environment regulates the structures and functions of cells, from the molecular to the tissue level. However, the underlying mechanisms influencing the organization and adaptation of cancer in 3D environments are not yet fully understood. In this study, we investigate the influence of the viscosity of the environment on the mechanical adaptability of human hepatoma cell (HepG2) spheroids in vitro, using 3D microcapsule reactors formed with droplet‐based microfluidics. To mimic the environment with different mechanical properties, HepG2 cells are encapsulated in alginate core‐shell reservoirs (i.e., microcapsules) with different core viscosities tuned by incorporating carboxymethylcellulose. The significant changes in cell and spheroid distribution, proliferation, and cytoskeleton are observed and quantified. Importantly, changes in the expression and distribution of F‐actin and keratin 8 indicate the relation between spheroid stiffness and viscosity of the surrounding medium. The increase of F‐actin levels in the viscous medium can indicate an enhanced ability of tumor cells to traverse dense tissue. These results demonstrate the ability of cancer cells to dynamically adapt to the changes in extracellular viscosity, which is an important physical cue regulating tumor development, and thus of relevance in cancer biology.This article is protected by copyright. All rights reserved

show abstract

Keratins determine network stress responsiveness in reconstituted actin–keratin filament systems

Abstract: The cytoskeleton is a major determinant of cell mechanics, and alterations in the central mechanical aspects of cells are observed during many pathological situations. Therefore, it is essential to investigate...

Cited by 24 publications

References 63 publications

Cells in Slow Motion: Apparent Undercooling Increases Glassy Behavior at Physiological Temperatures

Cells in Slow Motion: Apparent Undercooling Increases Glassy Behavior at Physiological Temperatures

Intermediate Filaments from Tissue Integrity to Single Molecule Mechanics

Impact of Viscosity on Human Hepatoma Spheroids in Soft Core–Shell Microcapsules

Contact Info

Product

Resources

About