Mechanics of the F-actin cytoskeleton

Stricker, Jonathan; Falzone, Tobias T.; Gardel, Margaret L.

doi:10.1016/j.jbiomech.2009.09.003

Cited by 414 publications

(363 citation statements)

References 67 publications

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“…On the molecular level, mechanical cell properties mainly depend on cytoskeletal fibrous structures (3), namely actin filaments, microtubules, and intermediate filaments (IFs). Although the contribution of actin filaments and microtubules to the resilience of many cell types is widely accepted (4), it has been hypothesized for many years that the resilience of epithelia against various types of deformation depends largely on keratins (5-7). These form a stable network spanning from the cell periphery to the nucleus.…”

mentioning

confidence: 99%

Keratins as the main component for the mechanical integrity of keratinocytes

Ramms

Fabris

Windoffer

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

190

187

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Keratins are major components of the epithelial cytoskeleton and are believed to play a vital role for mechanical integrity at the cellular and tissue level. Keratinocytes as the main cell type of the epidermis express a differentiation-specific set of type I and type II keratins forming a stable network and are major contributors of keratinocyte mechanical properties. However, owing to compensatory keratin expression, the overall contribution of keratins to cell mechanics was difficult to examine in vivo on deletion of single keratin genes. To overcome this problem, we used keratinocytes lacking all keratins. The mechanical properties of these cells were analyzed by atomic force microscopy (AFM) and magnetic tweezers experiments. We found a strong and highly significant softening of keratin-deficient keratinocytes when analyzed by AFM on the cell body and above the nucleus. Magnetic tweezers experiments fully confirmed these results showing, in addition, high viscous contributions to magnetic bead displacement in keratin-lacking cells. Keratin loss neither affected actin or microtubule networks nor their overall protein concentration. Furthermore, depolymerization of actin preserves cell softening in the absence of keratin. On reexpression of the sole basal epidermal keratin pair K5/14, the keratin filament network was reestablished, and mechanical properties were restored almost to WT levels in both experimental setups. The data presented here demonstrate the importance of keratin filaments for mechanical resilience of keratinocytes and indicate that expression of a single keratin pair is sufficient for almost complete reconstitution of their mechanical properties.

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mentioning

confidence: 99%

Keratins as the main component for the mechanical integrity of keratinocytes

Ramms

Fabris

Windoffer

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

190

187

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“…Lozupone et al (15) and Vico et al (16) revealed that cyclic environmental alterations may affect the structure and function of the cytoskeleton, including cytoskeletal reorganization, cytoskeletal fracture, cell dysfunction and cell death. F-actin is an important component of the cytoskeleton, and its integrity is a key factor in determining cell function (17). The present study demonstrated that the cell cytoskeleton depolymerized and rearranged with increasing mechanical force, indicating that mechanical stress may lead to F-actin damage in HPLFs.…”

Section: Discussionmentioning

confidence: 48%

Mechanical stress influences the viability and morphology of human parametrial ligament fibroblasts

Hong

et al. 2016

Molecular Medicine Reports

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Abstract. The present study aimed to investigate damage to human parametrial ligament fibroblasts by detecting cell proliferation, cytoskeletal structure, cellular alterations and senescence. Uterosacral and cardinal ligaments were obtained from 10 patients with cervical intraepithelial neoplasia grade II-III, who had received total vaginal hysterectomies, and fibroblasts were derived from this tissue. Fibroblasts were stretched using a four-point bending system with a force of 0 (control), 1,333 µ strain (1 mm) or 5,333 µ strain (4 mm) for 4 h. The present study revealed that mechanical force significantly reduced cell proliferation and increased cell senescence. As mechanical force increased, the mitochondria of fibroblasts began to exhibit vacuolization, and the cell cytoskeleton began to depolymerize and rearrange. In conclusion, the present study demonstrated that mechanical forces within a certain range may induce cell damage via mitochondrial injury, cytoskeletal alterations and increased cell senescence, resulting in decreased cell viability of pelvic fibroblasts.

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“…Actin bundles are observed to align primarily in parallel with the long axis of cells, which is very different from a disordered filament network Stricker et al, 2010). It seems that the alignment of actin bundles is of great importance to the mechanical properties of cells.…”

Section: Spread In Bundle Orientation To the Stretching Directionmentioning

confidence: 90%

“…Actin filament bundles are highorder cytoskeletal structures made of actin filaments packed together in concert with specific actin-binding proteins, like fascin and α-actinin (Tseng et al, 2005). In eukaryotic cells, actin filament bundle structures are common and include stress fibers, which are long and straight and align primarily in parallel with the long axis of the cell (Stricker et al, 2010). Shin et al (2004) reported that an actin bundle has a similar elastic modulus to that of a single actin filament, and an average bending stiffness more than two orders of magnitude larger than that of a bundle of uncrosslinked actin filaments.…”

Section: Introductionmentioning

confidence: 99%

Using a form-finding model to analyze the effect of actin bundles on the stiffness of a cytoskeleton network

Wang

Gong

2014

J. Zhejiang Univ. Sci. A

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Networks of actin filaments and bundles are ubiquitous in cellular cytoskeletons, but the elasticity of the network is not well understood. In this paper, a computational model based on form-finding analysis is proposed to investigate the stiffness of cytoskeleton networks consisting of actin filaments and bundles. The model shows that networks with parallel bundles aligned in the stretching direction are stiffer than those with randomly distributed bundles. The results provide a mechanical explanation for the experimental observation that cells primarily create parallel rather than disordered bundles during cell adhesion and cell motion. The effect of filament undulations on network stiffness is explored briefly. The results show that undulations can soften the network by increasing the bending-dominated deformations in filaments and bundles. Finally, we find that the effect of the relative density of bundles depends on their orientation. Increasing the density of randomly distributed bundles has no effect on the stiffness of cells, but softens the cytoskeleton network. In contrast, the stiffness of networks of parallel bundles first increases, then reduces as the relative density of bundles increases. The stiffest network is a mixture of actin filaments and bundles.

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Mechanics of the F-actin cytoskeleton

Cited by 414 publications

References 67 publications

Keratins as the main component for the mechanical integrity of keratinocytes

Keratins as the main component for the mechanical integrity of keratinocytes

Mechanical stress influences the viability and morphology of human parametrial ligament fibroblasts

Using a form-finding model to analyze the effect of actin bundles on the stiffness of a cytoskeleton network

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