Cytoplasmic intermediate filaments revealed as dynamic and multipurpose scaffolds

Coulombe, Pierre A.; Wong, Phil

doi:10.1038/ncb0804-699

Cited by 323 publications

(279 citation statements)

References 113 publications

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“…In many living cells, IFs form a dense network of filaments that provides passive mechanical support [5][6][7][8]. Mutations in IF genes are known to be the cause of several tissue fragility diseases, including the skin blistering disease epidermolysis bullosa simplex [6,9], which underscores the importance of IFs to maintaining the mechanical integrity of cells.…”

Section: Introductionmentioning

confidence: 99%

Regulation of hard α-keratin mechanics via control of intermediate filament hydration: matrix squeeze revisited

Greenberg

Fudge

2013

Proc. R. Soc. B.

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Mammalian hard a-keratins are fibre-reinforced biomaterials that consist of 10 nm intermediate filaments (IFs) embedded in an elastomeric protein matrix. Recent work suggests that the mechanical properties of IFs are highly sensitive to hydration, whereas hard a-keratins such as wool, hair and nail are relatively hydration insensitive. This raises the question of how mammalian keratins remain stiff in water. The matrix squeeze hypothesis states that the IFs in hard a-keratins are stiffened during an air-drying step during keratinization, and subsequently locked into a dehydrated state via the oxidation and cross-linking of the keratin matrix around them. The result is that even when hard a-keratins are immersed in water, their constituent IFs remain essentially 'dry' and therefore stiff. This hypothesis makes several predictions about the effects of matrix abundance and function on hard a-keratin mechanics and swelling behaviour. Specifically, it predicts that high matrix keratins in water will swell less, and have a higher tensile modulus, a higher yield stress and a lower dry-to-wet modulus ratio. It also predicts that disruption of the keratin matrix in water should lead to additional swelling, and a drop in modulus and yield stress. Our results are consistent with these predictions and suggest that the keratin matrix plays a critical role in governing the mechanical properties of mammalian keratins via control of IF hydration.

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Section: Introductionmentioning

confidence: 99%

Regulation of hard α-keratin mechanics via control of intermediate filament hydration: matrix squeeze revisited

Greenberg

Fudge

2013

Proc. R. Soc. B.

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“…Intermediate filaments (IFs) are key components of the cytoskeleton and help cells tolerate different forms of stresses from mechanical stress to exposure to heat, viruses, toxins, apoptosis inducing ligands, and other extrinsic cellular stresses (Pekny and Lane 2007;Diana et al 2005;Coulombe and Wong 2004). IF mutations cause or predispose to more than 30 human diseases, including skin diseases, muscular dystrophies, premature aging, amyotrophic lateral sclerosis, and end-stage liver disease (Omary et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Low concentration of GA activates a preconditioning response in HepG2 cells during oxidative stress—roles of Hsp90 and vimentin

Kang

Zou

2009

Cell Stress and Chaperones

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“…The NF network, which acts as a scaffold for microtubules, must be sufficiently flexible to allow for the transport of relatively large organelles (typically larger than the interfilament spacings) trafficking along microtubules immersed within the network [8][9][10][11] .…”

mentioning

confidence: 99%

Neurofilament sidearms modulate parallel and crossed-filament orientations inducing nematic to isotropic and re-entrant birefringent hydrogels

et al. 2013

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Neurofilaments are intermediate filaments assembled from the subunits neurofilament-low, neurofilament-medium and neurofilament-high. In axons, parallel neurofilaments form a nematic liquid-crystal hydrogel with network structure arising from interactions between the neurofilaments' C-terminal sidearms. Here we report, using small-angle X-ray-scattering, polarized-microscopy and rheometry, that with decreasing ionic strength, neurofilament-lowhigh, neurofilament-low-medium and neurofilament-low-medium-high hydrogels transition from the nematic hydrogel to an isotropic hydrogel (with random, crossed-filament orientation) and to an unexpected new re-entrant liquid-crystal hydrogel with parallel filaments-the bluish-opaque hydrogel-with notable mechanical and water retention properties reminiscent of crosslinked hydrogels. Significantly, the isotropic gel phase stability is sidearm-dependent: neurofilament-low-high hydrogels exhibit a wide ionic strength range, neurofilament-low-medium hydrogels a narrow ionic strength range, whereas neurofilamentlow hydrogels lack the isotropic gel phase. This suggests a dominant regulatory role for neurofilament-high sidearms in filament reorientation plasticity, facilitating organelle transport in axons. Neurofilament-inspired biomimetic hydrogels should therefore exhibit remarkable structure-dependent moduli and slow and fast water-release properties.

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Cytoplasmic intermediate filaments revealed as dynamic and multipurpose scaffolds

Cited by 323 publications

References 113 publications

Regulation of hard α-keratin mechanics via control of intermediate filament hydration: matrix squeeze revisited

Regulation of hard α-keratin mechanics via control of intermediate filament hydration: matrix squeeze revisited

Low concentration of GA activates a preconditioning response in HepG2 cells during oxidative stress—roles of Hsp90 and vimentin

Neurofilament sidearms modulate parallel and crossed-filament orientations inducing nematic to isotropic and re-entrant birefringent hydrogels

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