Intermediate filaments (IFs) formed by vimentin are less understood than their cytoskeletal partners, microtubules and F‐actin, but the unique physical properties of IFs, especially their resistance to large deformations, initially suggest a mechanical function. Indeed, vimentin IFs help regulate cell mechanics and contractility, and in crowded 3D environments they protect the nucleus during cell migration. Recently, a multitude of studies, often using genetic or proteomic screenings show that vimentin has many non‐mechanical functions within and outside of cells. These include signaling roles in wound healing, lipogenesis, sterol processing, and various functions related to extracellular and cell surface vimentin. Extracellular vimentin is implicated in marking circulating tumor cells, promoting neural repair, and mediating the invasion of host cells by viruses, including SARS‐CoV, or bacteria such as
The mechanical properties of the cellular nucleus are extensively studied as they play a critical role in important processes, such as cell migration, gene transcription, and stem cell differentiation. While the mechanical properties of the isolated nucleus have been tested, there is a lack of measurements about the mechanical behavior of the nucleus within intact cells and specifically about the interplay of internal nuclear components with the intracellular microenvironment, because current testing methods are based on contact and only allow studying the nucleus after isolation from a cell or disruption of cytoskeleton. Here, all‐optical Brillouin microscopy and 3D chemomechanical modeling are used to investigate the regulation of nuclear mechanics in physiological conditions. It is observed that the nuclear modulus can be modulated by epigenetic regulation targeting internal nuclear nanostructures such as lamin A/C and chromatin. It is also found that nuclear modulus is strongly regulated by cytoskeletal behavior through a robust mechanism conserved in different culturing conditions. Given the active role of cytoskeletal modulation in nearly all cell functions, this work will enable to reveal highly relevant mechanisms of nuclear mechanical regulations in physiological and pathological conditions.
more » « less- Award ID(s):
- 1929412
- NSF-PAR ID:
- 10457734
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Small
- Volume:
- 16
- Issue:
- 18
- ISSN:
- 1613-6810
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Listeria andStreptococcus . These findings underscore the fundamental role of vimentin in not only cell mechanics but also a range of physiological functions. Also see the video abstract herehttps://youtu.be/YPfoddqvz-g . -
Cytoskeleton morphology plays a key role in regulating cell mechanics. Particularly, cellular mechanical properties are directly regulated by the highly cross-linked and dynamic cytoskeletal structure of F-actin and microtubules presented in the cytoplasm. Although great efforts have been devoted to investigating the qualitative relation between the cellular cytoskeleton state and cell mechanical properties, comprehensive quantification results of how the states of F-actin and microtubules affect mechanical behavior are still lacking. In this study, the effect of both F-actin and microtubules morphology on cellular mechanical properties was quantified using atomic force microscope indentation experiments together with the proposed image recognition-based cytoskeleton quantification approach. Young’s modulus and diffusion coefficient of NIH/3T3 cells with different cytoskeleton states were quantified at different length scales. It was found that the living NIH/3T3 cells sense and adapt to the F-actin and microtubules states: both the cellular elasticity and poroelasticity are closely correlated to the depolymerization degree of F-actin and microtubules at all measured indentation depths. Moreover, the significance of the quantitative effects of F-actin and microtubules in affecting cellular mechanical behavior is depth-dependent.more » « less
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Key points Trabecular meshwork (TM) is a highly mechanosensitive tissue in the eye that regulates intraocular pressure through the control of aqueous humour drainage.
Its dysfunction underlies the progression of glaucoma but neither the mechanisms through which TM cells sense pressure nor their role in aqueous humour outflow are understood at the molecular level.
We identified the Piezo1 channel as a key TM transducer of tensile stretch, shear flow and pressure.
Its activation resulted in intracellular signals that altered organization of the cytoskeleton and cell‐extracellular matrix contacts and modulated the trabecular component of aqueous outflow whereas another channel, TRPV4, mediated a delayed mechanoresponse.
This study helps elucidate basic mechanotransduction properties that may contribute to intraocular pressure regulation in the vertebrate eye.
Abstract Chronic elevations in intraocular pressure (IOP) can cause blindness by compromising the function of trabecular meshwork (TM) cells in the anterior eye, but how these cells sense and transduce pressure stimuli is poorly understood. Here, we demonstrate functional expression of two mechanically activated channels in human TM cells. Pressure‐induced cell stretch evoked a rapid increase in transmembrane current that was inhibited by antagonists of the mechanogated channel Piezo1, Ruthenium Red and GsMTx4, and attenuated in Piezo1‐deficient cells. The majority of TM cells exhibited a delayed stretch‐activated current that was mediated independently of Piezo1 by TRPV4 (transient receptor potential cation channel, subfamily V, member 4) channels. Piezo1 functions as the principal TM transducer of physiological levels of shear stress, with both shear and the Piezo1 agonist Yoda1 increasing the number of focal cell‐matrix contacts. Analysis of TM‐dependent fluid drainage from the anterior eye showed significant inhibition by GsMTx4. Collectively, these results suggest that TM mechanosensitivity utilizes kinetically, regulatory and functionally distinct pressure transducers to inform the cells about force‐sensing contexts. Piezo1‐dependent control of shear flow sensing, calcium homeostasis, cytoskeletal dynamics and pressure‐dependent outflow suggests potential for a novel therapeutic target in treating glaucoma.
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