Regulatory Roles of Fluctuation-Driven Mechanotransduction in Cell Function

Suki, Bélâ; Parameswaran, Harikrishnan; Imsirovic, Jasmin; Bartolák‐Suki, Erzsébet

doi:10.1152/physiol.00051.2015

Cited by 24 publications

(20 citation statements)

References 141 publications

(160 reference statements)

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“…These same effects are seen in other collagenous soft tissues[28], and support the notion that IOP transients play an important role in the connective tissue remodeling signaling cascade. In addition, changes in ocular coat stiffness affect the magnitude of IOP transients[29], insofar as the eye is an elastic pressure vessel that can expand and contract to absorb some of the energy associated with transient events such as blink, saccade, and vascular pulse.…”

Section: Cellular Basis Of Ocular Connective Tissue Remodelingsupporting

confidence: 82%

Lamina cribrosa in glaucoma

Downs

Girkin

2017

Current Opinion in Ophthalmology

116

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Purpose of Review To present, summarize and interpret most recent advances in the study and understanding of the lamina cribrosa (LC) in glaucoma, in the context of previous work. Recent Findings The lamina is an active living structure that responds to strain and changes morphology at the micro- and macro-scales in glaucoma. Changes in LC morphology in glaucoma include posteriorization of the laminar insertion into the sclera, increased cupping or depth of the LC, and the development of focal LC defects. These LC changes are associated with disk hemorrhages and visual field damage, and are detectable with clinical imaging techniques such as optical coherence tomography (OCT). Glaucomatous changes in the LC are driven by cellular processes mediated by focal cyclical mechanical strain. Strain is eye specific and mediated by IOP, cerebrospinal fluid pressure (CSFP), and scleral and LC morphology and structural stiffness; deleterious LC strains can occur at all levels of mean IOP. Summary Laminar morphology is ever changing in health and disease, and recent studies have identified several promising morphological changes that are indicative of glaucoma susceptibility, onset and progression.

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Section: Cellular Basis Of Ocular Connective Tissue Remodelingsupporting

confidence: 82%

Lamina cribrosa in glaucoma

Downs

Girkin

2017

Current Opinion in Ophthalmology

116

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“…To explain these results, we first consider the amount of mechanical energy communicated to the cell during stretching. Assuming that cells can be considered a simple linearly elastic material, we have shown that the energy during variable stretching is related to the fluctuations in cycle-by-cycle amplitude 23 . The energy density during variable stretch (E VS ) can be written in the following form:…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the external mechanical environment is invariably noisy due for example to beat-to-beat blood pressure variability (BPV). Consequently, cells and their mitochondria also respond to fluctuations in mechanical factors, a process called fluctuation-driven mechanotransduction (FDM) 23 . Indeed, we recently reported that ATP production, monitored via the mitochondrial membrane potential, was maintained at a high level in vascular smooth muscle cells (VSMCs) when they were exposed to a variable-amplitude cyclic stretch pattern mimicking normal BPV compared with monotonous constant-amplitude cyclic stretch 24 .…”

mentioning

confidence: 99%

Tuning mitochondrial structure and function to criticality by fluctuation-driven mechanotransduction

Bartolák‐Suki

Suki

2020

Sci Rep

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Cells in vascular walls are exposed to blood pressure variability (BPV)-induced cycle-by-cycle fluctuations in mechanical forces which vary considerably with pathology. For example, BPV is elevated in hypertension but reduced under anesthesia. We hypothesized that the extent of mechanical fluctuations applied to vascular smooth muscle cells (VSMCs) regulates mitochondrial network structure near the percolation transition, which also influences ATP and reactive oxygen species (ROS) production. We stretched VSMCs in culture with cycle-by-cycle variability in area strain ranging from no variability (0%), as in standard laboratory conditions, through abnormally small (6%) and physiological (25%) to pathologically high (50%) variability mimicking hypertension, superimposed on 0.1 mean area strain. To explore how oxidative stress and ATP-dependent metabolism affect mitochondria, experiments were repeated in the presence of hydrogen peroxide and AMP-PNP, an ATP analog and competitive inhibitor of ATPases. Physiological 25% variability maintained activated mitochondrial cluster structure at percolation with a power law distribution and exponent matching the theoretical value in 2 dimensions. The 25% variability also maximized ATP and minimized cellular and mitochondrial ROS production via selective control of fission and fusion proteins (mitofusins, OPA1 and DRP1) as well as through stretch-sensitive regulation of the ATP synthase and VDAC1, the channel that releases ATP into the cytosol. Furthermore, pathologically low or high variability moved mitochondria away from percolation which reduced the effectiveness of the electron transport chain by lowering ATP and increasing ROS productions. We conclude that normal BPV is required for maintaining optimal mitochondrial structure and function in VSMCs.

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“…Integrin receptors perform both structural and mechanosensing signalling functions within cell-matrix adhesions. Integrins form heterodimers, consisting of an alpha and beta subunit [62] and are structurally comprised of an extracellular ligand-binding domain, which binds the ECM, and a cytosolic domain, which is anchored to the actin cytoskeleton [63] . Before transducing intracellular tension to the ECM, the integrin receptors must mature via the recruitment of further integrin receptors as well as other cytoskeletal components [64] .…”

Section: Cell-matrix Adhesionsmentioning

confidence: 99%

“…Before transducing intracellular tension to the ECM, the integrin receptors must mature via the recruitment of further integrin receptors as well as other cytoskeletal components [64] . Talin and alpha-actinin bind directly to the cytosolic domain of integrin and talin binding promotes the recruitment of additional components to cell matrix adhesions, including vinculin, paxillin and focal adhesion kinase [62,65] . Vinculin consists of 3-stuctural regions known as the head, neck and tail domain [66] .…”

Section: Cell-matrix Adhesionsmentioning

confidence: 99%

Vascular smooth muscle cell contractile function and mechanotransduction

Ahmed¹,

Warren²

2018

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Vascular smooth muscle cells (VSMCs) are the predominant cell type in the arterial wall and normally adopt a quiescent, contractile phenotype to regulate vascular tone. In the arterial wall, VSMCs are exposed to multiple mechanical cues, including stretch and matrix stiffness, which regulate VSMC contraction. However, during ageing and in vascular disease, such as atherosclerosis, hypertension and vascular calcification, the arterial wall stiffens and VSMC contraction contributes to this process. VSMCs display remarkable plasticity and changes in their mechanical environment promote VSMCs to adopt a proliferative, synthetic phenotype. VSMC phenotypic modulation is associated with altered expression of contractile proteins that generate actomyosin-based force. However, our understanding of precise mechanisms whereby altered mechanical landscape and mechanotransduction influence VSMC contraction remains limited. In this review, we discuss the present literature describing how VSMCs sense and respond to changes in their mechanical environment and how these changes influence VSMC contraction.

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Regulatory Roles of Fluctuation-Driven Mechanotransduction in Cell Function

Cited by 24 publications

References 141 publications

Lamina cribrosa in glaucoma

Lamina cribrosa in glaucoma

Tuning mitochondrial structure and function to criticality by fluctuation-driven mechanotransduction

Vascular smooth muscle cell contractile function and mechanotransduction

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