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https://www.readbyqxmd.com/read/28231640/mind-the-gap-mechanisms-regulating-the-endothelial-barrier
#1
REVIEW
Mariya Y Radeva, Jens Waschke
The endothelial barrier consists of intercellular contacts localized in the cleft between endothelial cells, which is covered by the glycocalyx in a sieve-like manner. Both types of barrier-forming junctions, i.e. the adherens junction (AJ) serving mechanical anchorage and mechanotransduction and the tight junction (TJ) sealing the intercellular space to limit paracelullar permeability, are tethered to the actin cytoskeleton. Under resting conditions, the endothelium thereby builds a selective layer controlling the exchange of fluid and solutes with the surrounding tissue...
February 23, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28230212/establishment-of-planar-cell-polarity-is-coupled-to-regional-cell-cycle-exit-and-cell-differentiation-in-the-mouse-utricle
#2
Xiaoyu Yang, Xiaoqing Qian, Rui Ma, Xinwei Wang, Juanmei Yang, Wenwei Luo, Ping Chen, Fanglu Chi, Dongdong Ren
Sensory hair cells are coordinately oriented within each inner ear sensory organ to exhibit a particular form of planar cell polarity (PCP) necessary for mechanotransduction. However, the developmental events associated with establishing PCP in the vestibule are unclear, hindering data interpretation and employment of the vestibule for PCP studies. Herein, we investigated PCP of the mouse vestibular organs. We further characterised cell cycle exit, cell differentiation, and PCP establishment in the utricle...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220498/the-role-of-apical-cell-cell-junctions-and-associated-cytoskeleton-in-mechanotransduction
#3
REVIEW
Sophie Sluysmans, Ekaterina Vasileva, Domenica Spadaro, Jimit Shah, Florian Rouaud, Sandra Citi
Tissues of multicellular organisms are characterized by several types of specialized cell-cell junctions. In vertebrate epithelia and endothelia, tight and adherens junctions play critical roles in barrier and adhesion functions, and are connected to the actin and microtubule cytoskeletons. The interaction between junctions and the cytoskeleton is crucial for tissue development and physiology, and is involved in the molecular mechanisms governing cell shape, motility, growth and signaling. The machineries which functionally connect tight and adherens junctions to the cytoskeleton comprise proteins which either bind directly to cytoskeletal filaments, or function as adaptors for regulators of the assembly and function of the cytoskeleton...
February 21, 2017: Biology of the Cell
https://www.readbyqxmd.com/read/28219986/functional-analysis-of-the-transmembrane-and-cytoplasmic-domains-of-pcdh15a-in-zebrafish-hair-cells
#4
Reo Maeda, Itallia V Pacentine, Timothy Erickson, Teresa Nicolson
Protocadherin 15 (PCDH15) is required for mechanotransduction in sensory hair cells as a component of the tip link. Isoforms of PCDH15 differ in their cytoplasmic domains (CD1, CD2, and CD3), but share the extracellular and transmembrane (TMD) domains, as well as an intracellular domain known as the common region (CR). In heterologous expression systems, both the TMD and CR of PCDH15 have been shown to interact with members of the mechanotransduction complex. The in vivo significance of these protein-protein interaction domains of PCDH15 in hair cells has not been determined...
February 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28211170/endothelial-glycocalyx-as-a-critical-signalling-platform-integrating-the-extracellular-haemodynamic-forces-and-chemical-signalling
#5
REVIEW
Ye Zeng
The glycocalyx covers the human mammalian cells and plays important roles in stroke, inflammation and atherosclerosis. It has also been shown to be involved in endothelial mechanotransduction of shear stress. Shear stress induces the remodelling of the major component of the glycocalyx including glypican-1, a cell membrane heparan sulphate proteoglycan. Other factors, such as sphingosine-1-phosphate (S1P), protect the glycocalyx against syndecan-1 ectodomain shedding and induce the synthesis of heparan sulphate...
February 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28209736/pejvakin-a-candidate-stereociliary-rootlet-protein-regulates-hair-cell-function-in-a-cell-autonomous-manner
#6
Marcin Kazmierczak, Piotr Kazmierczak, Anthony W Peng, Suzan L Harris, Prahar Shah, Jean-Luc Puel, Marc Lenoir, Santos J Franco, Martin Schwander
Mutations in the Pejvakin (PJVK) gene are thought to cause auditory neuropathy and hearing loss of cochlear origin by affecting noise-induced peroxisome proliferation in auditory hair cells and neurons. Here we demonstrate that loss of pejvakin in hair cells, but not in neurons, causes profound hearing loss and outer hair cell degeneration in mice. Pejvakin binds to and co-localizes with the rootlet component TRIOBP at the base of stereocilia in injectoporated hair cells, a pattern that is disrupted by deafness-associated PJVK mutations...
February 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28205330/effect-of-matrix-stiffness-on-osteoblast-functionalization
#7
Tao Zhang, Shiyu Lin, Xiaoru Shao, Qi Zhang, Changyue Xue, Shu Zhang, Yunfeng Lin, Bofeng Zhu, Xiaoxiao Cai
OBJECTIVES: Stiffness of bone tissue differs response to its physiological or pathological status, such as osteoporosis or osteosclerosis. Consequently, the function of cells residing in bone tissue including osteoblasts (OBs), osteoclasts and osteocytes will be affected. However, to the best of our knowledge, the detailed mechanism of how extracellular matrix stiffness affects OB function remains unclear. MATERIALS AND METHODS: We conducted a study that exposed rat primary OBs to polydimethylsiloxane substrates with varied stiffness to investigate the alterations of cell morphology, osteoblastic differentiation and its potential mechanism in mechanotransduction...
February 15, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28192301/dynamic-interaction-between-actin-and-nesprin2-maintain-the-cell-nucleus-in-a-prestressed-state
#8
Abhishek Kumar, G V Shivashankar
Mechanical coupling between the nucleus and the cytoskeleton is indispensable for direct force transduction from the extra cellular matrix (ECM) to the chromatin. Although this physical coupling has been shown to be crucial for nuclear positioning and its function, the quantification of nuclear-cytoskeleton interaction has been lacking. In this paper, using various quantitative fluorescence spectroscopy techniques, we investigate the nature of this connection. High-resolution 3D imaging shows that nesprin2G forms short linear structures along actin stress fibers (ASFs) in the apical region of the nucleus...
November 11, 2016: Methods and Applications in Fluorescence
https://www.readbyqxmd.com/read/28191820/vascular-smooth-muscle-cell-glycocalyx-mediates-shear-stress-induced-contractile-responses-via-a-rho-kinase-rock-myosin-light-chain-phosphatase-mlcp-pathway
#9
Hongyan Kang, Jiajia Liu, Anqiang Sun, Xiao Liu, Yubo Fan, Xiaoyan Deng
The vascular smooth muscle cells (VSMCs) are exposed to interstitial flow induced shear stress that may be sensed by the surface glycocalyx, a surface layer composed primarily of proteoglycans and glycoproteins, to mediate cell contraction during the myogenic response. We, therefore, attempted to elucidate the signal pathway of the glycocalyx mechanotransduction in shear stress regulated SMC contraction. Human umbilical vein SMCs (HUVSMCs) deprived of serum for 3-4 days were exposed to a step increase (0 to 20 dyn/cm(2)) in shear stress in a parallel plate flow chamber, and reduction in the cell area was quantified as contraction...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28186467/effect-of-the-microenvironment-on-mesenchymal-stem-cells-paracrine-signalling-opportunities-to-engineer-the-therapeutic-effect
#10
Gina Diamanta Kusuma, James Carthew, Rebecca Lim, Jessica Ellen Frith
Cues from the extracellular environment, including physical stimuli, are well known to affect mesenchymal stem cells (MSCs) properties in terms of proliferation and differentiation. Many therapeutic strategies are now targeting this knowledge to increase the efficacy of cell therapies, typically employed to repair tissue functions in the event of injury, either by direct engraftment into the target tissue or differentiation into mature tissues. However, it is now envisioned that harnessing the repertoire of factors secreted by MSCs (termed the secretome) may provide an alternate to these cell therapies...
February 10, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28186127/optogenetic-control-of-cellular-forces-and-mechanotransduction
#11
Léo Valon, Ariadna Marín-Llauradó, Thomas Wyatt, Guillaume Charras, Xavier Trepat
Contractile forces are the end effectors of cell migration, division, morphogenesis, wound healing and cancer invasion. Here we report optogenetic tools to upregulate and downregulate such forces with high spatiotemporal accuracy. The technology relies on controlling the subcellular activation of RhoA using the CRY2/CIBN light-gated dimerizer system. We fused the catalytic domain (DHPH domain) of the RhoA activator ARHGEF11 to CRY2-mCherry (optoGEF-RhoA) and engineered its binding partner CIBN to bind either to the plasma membrane or to the mitochondrial membrane...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28169278/improving-the-therapeutic-efficacy-of-mesenchymal-stromal-cells-to-restore-perfusion-in-critical-limb-ischemia-through-pulsed-focused-ultrasound
#12
Pamela A Tebebi, Saejeong J Kim, Rashida A Williams, Blerta Milo, Victor Frenkel, Scott R Burks, Joseph A Frank
Mesenchymal stem cells (MSC) are promising therapeutics for critical limb ischemia (CLI). Mechanotransduction from pulsed focused ultrasound (pFUS) upregulates local chemoattractants to enhance homing of intravenously (IV)-infused MSC and improve outcomes. This study investigated whether pFUS exposures to skeletal muscle would improve local homing of iv-infused MSCs and their therapeutic efficacy compared to iv-infused MSCs alone. CLI was induced by external iliac arterial cauterization in 10-12-month-old mice...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28167863/biomechanical-cell-regulatory-networks-as-complex-adaptive-systems-in-relation-to-cancer
#13
REVIEW
Liviu Feller, Razia Abdool Gafaar Khammissa, Johan Lemmer
Physiological structure and function of cells are maintained by ongoing complex dynamic adaptive processes in the intracellular molecular pathways controlling the overall profile of gene expression, and by genes in cellular gene regulatory circuits. Cytogenetic mutations and non-genetic factors such as chronic inflammation or repetitive trauma, intrinsic mechanical stresses within extracellular matrix may induce redirection of gene regulatory circuits with abnormal reactivation of embryonic developmental programmes which can now drive cell transformation and cancer initiation, and later cancer progression and metastasis...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28164414/microfluidic-traction-force-microscopy-to-study-mechanotransduction-in-angiogenesis
#14
Luke Boldock, Claudia Wittkowske, Cecile M Perrault
The formation of new blood vessels from existing vasculature, angiogenesis, is driven by coordinated endothelial cell migration and matrix remodelling in response to local signals. Recently, a growing body of evidence has shown that mechanotransduction, along with chemotransduction, is a major regulator of angiogenesis. Mechanical signals, such as fluid shear stress and substrate mechanics, influence sprouting and network formation, but the mechanisms behind this relationship are still unclear. Here, we present cellular traction forces as possible effectors activated by mechanosensing to mediate matrix remodelling, and encourage the use of traction force microscopy to study mechanotransduction in angiogenesis...
February 6, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28155694/%C3%AE-1-integrin-signaling-in-asymmetric-migration-of-keratinocytes-under-mechanical-stretch-in-a-co-cultured-wound-repair-model
#15
Dongyuan Lü, Zhan Li, Yuxin Gao, Chunhua Luo, Fan Zhang, Lu Zheng, Jiawen Wang, Shujin Sun, Mian Long
BACKGROUND: Keratinocyte (KC) migration in re-epithelization is crucial in repairing injured skin. But the mechanisms of how mechanical stimuli regulate the migration of keratinocytes have been poorly understood. METHODS: Human immortalized keratinocyte HaCaT cells were co-cultured with skin fibroblasts on PDMS membranes and transferred to the static stretch device developed in-house for additional 6 day culture under mechanical stretch to mimic surface tension in skin...
December 28, 2016: Biomedical Engineering Online
https://www.readbyqxmd.com/read/28152338/dynamic-regulation-of-nuclear-architecture-and-mechanics-a-rheostatic-role-for-the-nucleus-in-tailoring-cellular-mechanosensitivity
#16
Stephen D Thorpe, David A Lee
Nuclear architecture, a function of both chromatin and nucleoskeleton structure, is known to change with stem cell differentiation and differs between various somatic cell types. These changes in nuclear architecture are associated with the regulation of gene expression and genome function in a cell-type specific manner. Biophysical stimuli are known effectors of differentiation and also elicit stimuli-specific changes in nuclear architecture. This occurs via the process of mechanotransduction whereby extracellular mechanical forces activate a number of well characterised signalling cascades of cytoplasmic origin, and potentially some recently elucidated signalling cascades originating in the nucleus...
February 2, 2017: Nucleus
https://www.readbyqxmd.com/read/28148497/shear-stress-induces-g%C3%AE-q-11-activation-independent-of-g-protein-coupled-receptor-activation-in-endothelial-cells
#17
Nathaniel G Dela Paz, Benoît Melchior, John A Frangos
Mechanochemical signal transduction occurs when mechanical forces, such as fluid shear stress, are converted into biochemical responses within the cell. The molecular mechanisms by which endothelial cells (ECs) sense/transduce shear stress into biological signals, including the nature of the mechanosensor, are still unclear. G proteins and G protein-coupled receptors (GPCRs) have been postulated independently to mediate mechanotransduction. In this study, we used in situ proximity ligation assay (PLA) to investigate the role of a specific GPCR/Gαq/11 pair in EC shear stress-induced mechanotransduction...
February 1, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28147641/monitoring-in-real-time-focal-adhesion-protein-dynamics-in-response-to-a-discrete-mechanical-stimulus
#18
Catalina von Bilderling, Martín Caldarola, Martín E Masip, Andrea V Bragas, Lía I Pietrasanta
The adhesion of cells to the extracellular matrix is a hierarchical, force-dependent, multistage process that evolves at several temporal scales. An understanding of this complex process requires a precise measurement of forces and its correlation with protein responses in living cells. We present a method to quantitatively assess live cell responses to a local and specific mechanical stimulus. Our approach combines atomic force microscopy with fluorescence imaging. Using this approach, we evaluated the recruitment of adhesion proteins such as vinculin, focal adhesion kinase, paxillin, and zyxin triggered by applying forces in the nN regime to live cells...
January 2017: Review of Scientific Instruments
https://www.readbyqxmd.com/read/28138960/high-glucose-alters-the-secretome-of-mechanically-stimulated-osteocyte-like-cells-affecting-osteoclast-precursor-recruitment-and-differentiation
#19
Marta Maycas, María Teresa Portolés, María Concepción Matesanz, Irene Buendía, Javier Linares, María José Feito, Daniel Arcos, María Vallet-Regí, Lilian Plotkin, Pedro Esbrit, Arancha R Gortázar
Diabetes mellitus (DM) induces bone deterioration, while mechanical stimulation promotes osteocyte-driven bone formation. We aimed to evaluate the interaction of acute exposure (24h) to high glucose (HG) with both the pro-survival effect conferred to osteocytic MLO-Y4 cells and osteoblastic MC3T3-E1 cells by mechanical stimulation and the interaction of these cells with osteoclast precursor RAW264.7 cells. We found that 24h of HG (25 mM) pre-exposure prevented both cell survival and ERK and β-catenin nuclear translocation upon mechanical stimulation by fluid flow (FF) (10 min) in both MLO-Y4 and MC3T3-E1 cells...
January 31, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28135189/direct-measurement-of-trpv4-and-piezo1-activity-reveals-multiple-mechanotransduction-pathways-in-chondrocytes
#20
M Rocio Servin-Vences, Mirko Moroni, Gary R Lewin, Kate Poole
The joints of mammals are lined with cartilage, comprised of individual chondrocytes embedded in a specialized extracellular matrix. Chondrocytes experience a complex mechanical environment and respond to changing mechanical loads in order to maintain cartilage homeostasis. It has been proposed that mechanically gated ion channels are of functional importance in chondrocyte mechanotransduction; however, direct evidence of mechanical current activation in these cells has been lacking. We have used high-speed pressure clamp and elastomeric pillar arrays to apply distinct mechanical stimuli to primary murine chondrocytes, stretch of the membrane and deflection of cell-substrate contacts points, respectively...
January 30, 2017: ELife
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