Search results for "mechanotransduction"

Shear Stress and Aortic Strain Associations With Biomarkers of Ascending Thoracic Aortic Aneurysm

2019

This study aims to investigate the association of wall shear stress (WSS) and aortic strain with circulating biomarkers including matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinase (TIMP), and exosomal level of microRNA (miRNA) in ascending aortic aneurysms of patients with bicuspid or tricuspid aortic valve.A total of 76 variables from 125 patients with ascending aortic aneurysms were collected from (1) blood plasma to measure plasma levels of miRNAs and protein activity; (2) computational flow analysis to estimate peak systolic WSS and time-average WSS (TAWSS); and (3) imaging analysis of computed tomography angiography to determine aortic wall strain. Principal compo…

The influence of a depressed scapular alignment on upper limb neural tissue mechanosensitivity and local pressure pain sensitivity

2017

A depressed scapular alignment could lead to prolonged and repetitive stress or compression of the brachial plexus, resulting in sensitization of neural tissue. However, no study has investigated the influence of alignment of the scapulae on sensitization of upper limb neural tissue in otherwise asymptomatic people. In this case-control study, we investigate the influence of a depressed scapular alignment on mechanosensitivity of the upper limb peripheral nervous system as well as pressure pain thresholds (PPT). Asymptomatic individuals with neutral vertical scapular alignment (n = 25) or depressed scapular alignment (n = 25) participated. We measured the upper limb neurodynamic test (ULNT1…

YAP/TAZ activity in stromal cells prevents ageing by controlling cGAS-STING

2022

Ageing is intimately connected to the induction of cell senescence(1,2), but why this is so remains poorly understood. A key challenge isthe identification of pathways that normally suppress senescence, are lost during ageing and are functionally relevant to oppose ageing(3). Here we connected the structural and functional decline of ageing tissues to attenuated function of the master effectors of cellular mechanosignalling YAP and TAZ. YAP/TAZ activity declines during physiological ageing in stromal cells, and mimicking such decline through genetic inactivation of YAP/TAZ in these cells leads to accelerated ageing. Conversely, sustaining YAP function rejuvenates old cells and opposes the e…

Thermal sensation and cell adaptability

2013

Whole person adaptive comfort is discussed with reference to recent findings in molecular scale systems biology. The observations are upscaled to hypotheses relating to less traditional interpretations of thermal processes, which have new implications for indoor climate management and design. Arguments are presented for a revision of current focus, model and paradigm. The issue is seen as a problem of integrating theoretical development, conceptual modeling and as an investigation of the extent to which environments and acclimatization can be used to achieve individual fitness and health, not only at the subjective comfort level, as hitherto promoted. It is argued that there are many questi…

Tissue fluidification promotes a cGAS-STING cytosolic DNA response in invasive breast cancer.

2022

: The process in which locally confined epithelial malignancies progressively evolve into invasive cancers is often promoted by unjamming, a phase transition from a solid-like to a liquid-like state, which occurs in various tissues. Whether this tissue-level mechanical transition impacts phenotypes during carcinoma progression remains unclear. Here we report that the large fluctuations in cell density that accompany unjamming result in repeated mechanical deformations of cells and nuclei. This triggers a cellular mechano-protective mechanism involving an increase in nuclear size and rigidity, heterochromatin redistribution and remodelling of the perinuclear actin architecture into actin rin…

Biotensegrity of the Extracellular Matrix: Physiology, Dynamic Mechanical Balance, and Implications in Oncology and Mechanotherapy

2014

Cells have the capacity to convert mechanical stimuli into chemical changes. This process is based on the tensegrity principle, a mechanism of tensional integrity. To date, this principle has been demonstrated to act in physiological processes such as mechanotransduction and mechanosensing at different scales (from cell sensing through integrins to molecular mechanical interventions or even localized massage). The process involves intra- and extracellular components, including the participation of extracellular matrix (ECM) and microtubules that act as compression structures, and actin filaments which act as tension structures. The nucleus itself has its own tensegrity system which is impli…

Deleting Full Length Titin Versus the Titin M-Band Region Leads to Differential Mechanosignaling and Cardiac Phenotypes

2019

Background: Titin is a giant elastic protein that spans the half-sarcomere from Z-disk to M-band. It acts as a molecular spring and mechanosensor and has been linked to striated muscle disease. The pathways that govern titin-dependent cardiac growth and contribute to disease are diverse and difficult to dissect. Methods: To study titin deficiency versus dysfunction, the authors generated and compared striated muscle specific knockouts (KOs) with progressive postnatal loss of the complete titin protein by removing exon 2 (E2-KO) or an M-band truncation that eliminates proper sarcomeric integration, but retains all other functional domains (M-band exon 1/2 [M1/2]-KO). The authors evaluated c…

2020

Cilia are cellular organelles that project from the cell. They occur in nearly all non-hematopoietic tissues and have different functions in different tissues. In mesenchymal tissues primary cilia play a crucial role in the adequate morphogenesis during embryological development. In mature articular cartilage, primary cilia fulfil chemo- and mechanosensitive functions to adapt the cellular mechanisms on extracellular changes and thus, maintain tissue homeostasis and morphometry. Ciliary abnormalities in osteoarthritic cartilage could represent pathophysiological relationships between ciliary dysfunction and tissue deformation. Nevertheless, the molecular and pathophysiological relationships…

Physiological Micromechanics of the Anterior Mitral Valve Leaflet

2011

An improved understanding of mitral valve (MV) function remains an important goal for determining mechanisms underlying valve disease and for developing novel therapies. Critical to heart valve tissue homeostasis is the valvular interstitial cells (VICs), which reside in the interstitium and maintain the extracellular matrix (ECM) through both protein synthesis and enzymatic degradation [1]. There is scant experimental data on the alterations of the MV fiber network reorganization as a function of load, which is critical for implementation of computational strategies that attempt to link this meso-micro scale phenomenon. The observed large scale deformations experienced by VICs could be imp…

Alterations in the Microstructure of the Anterior Mitral Valve Leaflet Under Physiological Stress

2012

An improved understanding of mitral valve (MV) function remains an important goal for determining mechanisms underlying valve disease and for developing novel therapies. Critical to heart valve tissue homeostasis is the valvular interstitial cells (VICs), which reside in the interstitium and maintain the extracellular matrix (ECM) through both protein synthesis and enzymatic degradation [1]. There is scant quantitative experimental data on the alterations of the MV fiber network reorganization as a function of load, which is critical for implementation of computational strategies that attempt to link this meso-micro scale phenomenon. The observed large scale deformations experienced by VICs…