Compressive forces stabilize microtubules in living cells

Li, Yuhui; Kučera, Ondřej; Cuvelier, Damien; Rutkowski, David M.; Deygas, Mathieu; Rai, Dipti; Pavlovič, Tonja; Vicente, Filipe Nunes; Piel, Matthieu; Giannone, Grégory; Vavylonis, Dimitrios; Akhmanova, Anna; Blanchoin, Laurent; Théry, Manuel

doi:10.1038/s41563-023-01578-1

Cited by 28 publications

(17 citation statements)

References 86 publications

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“…3 B). Furthermore, stretched cells exhibited a higher β-tubulin to acetylated tubulin ratio, implying mechanical stretch may augment tubulin polymerization and acetylation, thus stimulating microtubule dynamics and cytoskeletal remodeling [ 51 ].…”

Section: Resultsmentioning

confidence: 99%

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Cyclic stretch induced epigenetic activation of periodontal ligament cells

Bae,

Shin,

et al. 2024

Materials Today Bio

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Section: Resultsmentioning

confidence: 99%

“…ECM stiffness was also closely related to the epigenetics of histones in the nucleus [ 68 ]. When compression occurs, microtubules play a role in stabilizing the cell [ 51 ]. However, further research is needed to determine whether these responses occur in the same way in the PDL.…”

Section: Resultsmentioning

confidence: 99%

Cyclic stretch induced epigenetic activation of periodontal ligament cells

Bae,

Shin,

et al. 2024

Materials Today Bio

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“…Importantly, the cytoskeleton is the main mechanism by which mechanical force is transmitted within and between cells, and often remodels in response to mechanical stimuli 23 . Recent reports indicated the MT cytoskeleton is stabilized by force to protect confined cells from damage [24][25][26][27] . We hypothesized that melanoma cells hijack neuronal mechanisms to allow them to invade into the mechanically confined microenvironment.…”

Section: The Microtubule Cytoskeleton Hijacks Neuronal Mechanisms To ...mentioning

confidence: 99%

“…To investigate how mechanical confinement induces HMGB2 upregulation, we focused on the MT cytoskeleton due to its role in mechanotransduction [24][25][26][27] , hypothesizing that the perinuclear acetylated tubulin network ( Fig. 2f-g ) may function to propagate confinement-induced mechanical force to the nucleus.…”

Section: Hmgb2 Upregulation Is Mediated By the Perinuclear Acetylated...mentioning

confidence: 99%

Mechanical confinement governs phenotypic plasticity in melanoma

Hunter,

Montal,

et al. 2024

Preprint

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Phenotype switching is a form of cellular plasticity in which cancer cells reversibly move between two opposite extremes - proliferative versus invasive states. While it has long been hypothesised that such switching is triggered by external cues, the identity of these cues has remained elusive. Here, we demonstrate that mechanical confinement mediates phenotype switching through chromatin remodelling. Using a zebrafish model of melanoma coupled with human samples, we profiled tumor cells at the interface between the tumor and surrounding microenvironment. Morphological analysis of these rare cells showed flattened, elliptical nuclei suggestive of mechanical confinement by adjacent tissue. Spatial and single-cell transcriptomics demonstrated that the interface cells adopted a gene program of neuronal invasion, including acquisition of an acetylated tubulin cage that protects the nucleus during migration. We identified the DNA-bending protein HMGB2 as a confinement-induced mediator of the neuronal state. HMGB2 is upregulated in confined cells, and quantitative modelling revealed that confinement prolongs contact time between HMGB2 and chromatin, leading to changes in chromatin configuration that favor the neuronal phenotype. Genetic disruption of HMGB2 showed that it regulates the trade-off between proliferative and invasive states, in which confined HMGB2hightumor cells are less proliferative but more drug resistant. Our results implicate the mechanical microenvironment as a mechanism driving phenotype switching in melanoma.

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“…[ 269 ] By contrast, increasing compressive forces stabilize microtubules in living cells, which is instrumental for maintaining cell shape and migration in confined space. [ 270 ] Additionally, stiff substrates, increased F‐actin contractility, and FA expansion enhance microtubule acetylation, [ 101 ] whereas a temporally stiffening substrate leads to microtubule deacetylation. [ 112 ] Recent studies also indicate the involvement of spectrin, [ 271 ] keratin, and vimentin cytoskeletons [ 272 ] in cellular mechanotransduction.…”

Section: Mechanotransduction At the Subcellular And Molecular Levelsmentioning

confidence: 99%

A Hierarchical Mechanotransduction System: From Macro to Micro

Cao,

Tian,

Tian

et al. 2023

Advanced Science

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Mechanotransduction is a strictly regulated process whereby mechanical stimuli, including mechanical forces and properties, are sensed and translated into biochemical signals. Increasing data demonstrate that mechanotransduction is crucial for regulating macroscopic and microscopic dynamics and functionalities. However, the actions and mechanisms of mechanotransduction across multiple hierarchies, from molecules, subcellular structures, cells, tissues/organs, to the whole‐body level, have not been yet comprehensively documented. Herein, the biological roles and operational mechanisms of mechanotransduction from macro to micro are revisited, with a focus on the orchestrations across diverse hierarchies. The implications, applications, and challenges of mechanotransduction in human diseases are also summarized and discussed. Together, this knowledge from a hierarchical perspective has the potential to refresh insights into mechanotransduction regulation and disease pathogenesis and therapy, and ultimately revolutionize the prevention, diagnosis, and treatment of human diseases.

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Compressive forces stabilize microtubules in living cells

Cited by 28 publications

References 86 publications

Cyclic stretch induced epigenetic activation of periodontal ligament cells

Cyclic stretch induced epigenetic activation of periodontal ligament cells

Mechanical confinement governs phenotypic plasticity in melanoma

A Hierarchical Mechanotransduction System: From Macro to Micro

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