The nuclear envelope as a mechanostat: a central cog in the machinery of
                        cell and tissue regulation?

Snedeker, Jess G.

doi:10.1038/bonekey.2014.57

Cited by 3 publications

(8 citation statements)

References 22 publications

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“…It has been demonstrated that mechanical distortion of the cell nucleus provokes a relative shift in nuclear envelope composition [109]. This change is not only associated with very direct modulation of several important cell signaling pathways [135], but may more generally regulate gene expression by physically modulating chromatin accessibility -potentially acting as a molecular ''state switch" [110]. While tendon nuclei have been established to deform under tissue loading [136], a current challenge is to unravel the implications of these deformations.…”

Section: Nuclear Deformationsmentioning

confidence: 99%

“…shear stresses from fluid flow and fascicle sliding, tensile stresses from direct elongation of collagen structures and hydrostatic stresses from the volumetric changes with external loading [116,138,139]. These mechanical stresses are responsible for the activation of candidate ''vectors" by which tendon cells can potentially ''transduce" mechanical forces within the tissue to regulate cell signaling and behavior: 1) stretch activated ion channels (SACs) as mechanosensitive ion channels, 2) focal adhesion-mediated mechanical signal transduction, 3) the primary cilium and 4) nuclear deformations [109][110][111][112][113]116]. Fig.…”

Section: Focal Adhesion-mediated Mechanical Signal Transductionmentioning

confidence: 99%

“…Tendon cells feature various cellular machineries for sensing a range of distinct mechanical stimuli within their matrix (Fig. 5) [108][109][110]. A cell can rapidly respond to tension and shear by adjusting its physical coupling to its local matrix [111,112], or by remodeling its cytoskeleton [113].…”

Section: The Tendon Cell As a Mechanical Sensor And Arbiter Of Tendonmentioning

confidence: 99%

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Tendon injury and repair – A perspective on the basic mechanisms of tendon disease and future clinical therapy

2017

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Section: Nuclear Deformationsmentioning

confidence: 99%

Section: Focal Adhesion-mediated Mechanical Signal Transductionmentioning

confidence: 99%

Section: The Tendon Cell As a Mechanical Sensor And Arbiter Of Tendonmentioning

confidence: 99%

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Tendon injury and repair – A perspective on the basic mechanisms of tendon disease and future clinical therapy

2017

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“…This way excessive deformation of the nuclei under intermittent mechanical load could be prevented. The ability of the nucleus with an intact permeability barrier to buffer intermittent mechanical loads provides the missing short‐term component of the intracellular mechanostat function of the nucleus . Taken together, our proposed model predicts that the external forces acting on the nucleus can be counterbalanced by the colloid‐osmotic mismatch across the nuclear envelope generated by both the transport and the barrier function of the NPCs.…”

Section: Resultsmentioning

confidence: 81%

“…The ability of the nucleus with an intact permeability barrier to buffer intermittent mechanical loads provides the missing short-term component of the intracellular mechanostat function of the nucleus. [25,34] Taken together, our proposed model predicts that the external forces acting on the nucleus can be counterbalanced by the colloidosmotic mismatch across the nuclear envelope generated by both the transport and the barrier function of the NPCs. Critically, those force cannot exceed the upper mechanical limit of the nuclear envelope imposed by the level of lamin A/C expression.…”

Section: Integration Of the Nuclear Envelope Transport And Barrier Fumentioning

confidence: 80%

Nuclear Envelope Permeability Barrier as a Fast‐Response Intracellular Mechanostat

et al. 2019

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The nuclear envelope is an undisputed component of the intracellular mechanotransduction cascades which collect, process, and respond to mechanical stimuli from the environment. At the same time, the nuclear envelope performs the function of a selective barrier between the nuclear and cytoplasmic compartments. Although the mechanosensing and the barrier functions of the nuclear envelope have both been subjects of intense research, a possible reciprocal relationship between them is only beginning to emerge. In this report, the role of the nucleocytoplasmic permeability barrier is evaluated in nuclear mechanics. Using a combination of atomic force and confocal microscopy, the functional state of the nucleocytoplasmic permeability barrier and the nuclear mechanics is monitored. By modulating the stringency of the barrier and simulating the active transport imbalance across the nuclear envelope, the decisive impact of these parameters on nuclear mechanics is demonstrated. It is concluded that the nucleocytoplasmic barrier is the second essential component of the intracellular mechanostat function performed by the nuclear envelope.

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Aqueous outflow regulation – 21st century concepts

Johnstone

Chen

Tan

et al. 2021

Progress in Retinal and Eye Research

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We propose an integrated model of aqueous outflow control that employs a pump-conduit system in this article. Our model exploits accepted physiologic regulatory mechanisms such as those of the arterial, venous, and lymphatic systems. Here, we also provide a framework for developing novel diagnostic and therapeutic strategies to improve glaucoma patient care. In the model, the trabecular meshwork distends and recoils in response to continuous physiologic IOP transients like the ocular pulse, blinking, and eye movement. The elasticity of the trabecular meshwork determines cyclic volume changes in Schlemm’s canal (SC). Tube-like SC inlet valves provide aqueous entry into the canal, and outlet valve leaflets at collector channels control aqueous exit from SC. Connections between the pressure-sensing trabecular meshwork and the outlet valve leaflets dynamically control flow from SC. Normal function requires regulation of the trabecular meshwork properties that determine distention and recoil. The aqueous pump-conduit provides short-term pressure control by varying stroke volume in response to pressure changes. Modulating TM constituents that regulate stroke volume provides long-term control. The aqueous outflow pump fails in glaucoma due to the loss of trabecular tissue elastance, as well as alterations in ciliary body tension. These processes lead to SC wall apposition and loss of motion. Visible evidence of pump failure includes a lack of pulsatile aqueous discharge into aqueous veins and reduced ability to reflux blood into SC. These alterations in the functional properties are challenging to monitor clinically. Phase-sensitive OCT now permits noninvasive, quantitative measurement of pulse-dependent TM motion in humans. This proposed conceptual model and related techniques offer a novel framework for understanding mechanisms, improving management, and development of therapeutic options for glaucoma.

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The nuclear envelope as a mechanostat: a central cog in the machinery of cell and tissue regulation?

Cited by 3 publications

References 22 publications

Tendon injury and repair – A perspective on the basic mechanisms of tendon disease and future clinical therapy

Tendon injury and repair – A perspective on the basic mechanisms of tendon disease and future clinical therapy

Nuclear Envelope Permeability Barrier as a Fast‐Response Intracellular Mechanostat

Aqueous outflow regulation – 21st century concepts

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