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Kathryn M Kingsmore, Daniel K Logsdon, Desiree H Floyd, Shayn M Peirce, Benjamin W Purow, Jennifer M Munson
Glioblastoma (GBM) prognosis remains dismal due in part to the invasiveness of GBM cells. Interstitial fluid flow (IFF) has been shown to increase invasion of glioma cells in vitro through the CXCR4 receptor interacting with autologous, pericellular gradients of CXCL12 (autologous chemotaxis) or through the CD44 receptor interactions with the extracellular matrix (hyaluronan-mediated mechanotransduction). These mechanisms have not been examined together and thus we hypothesized that both mechanisms contribute to invasion in populations of cancer cells...
October 24, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Zakieh Alihemmati, Bahman Vahidi, Nooshin Haghighipour, Mohammad Salehi
It has been found that cells react to mechanical stimuli, while the type and magnitude of these cells are different in various physiological and pathological conditions. These stimuli may affect cell behaviors via mechanotransduction mechanisms. The aim of this study is to evaluate mechanical responses of a mesenchymal stem cell (MSC) to a pressure loading using finite elements method (FEM) to clarify procedures of MSC mechanotransduction. The model is constructed based on an experimental set up in which statics and cyclic compressive loads are implemented on a model constructed from a confocal microscopy 3D image of a stem cell...
January 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
Rebecca L Lamason, Effie Bastounis, Natasha M Kafai, Ricardo Serrano, Juan C Del Álamo, Julie A Theriot, Matthew D Welch
Spotted fever group (SFG) rickettsiae are human pathogens that infect cells in the vasculature. They disseminate through host tissues by a process of cell-to-cell spread that involves protrusion formation, engulfment, and vacuolar escape. Other bacterial pathogens rely on actin-based motility to provide a physical force for spread. Here, we show that SFG species Rickettsia parkeri typically lack actin tails during spread and instead manipulate host intercellular tension and mechanotransduction to promote spread...
October 20, 2016: Cell
Subarna Dutta, Maitree Bhattacharyya, Kaushik Sengupta
Lamins are mechanosensitive and elastic components of the nuclear lamina that respond to external mechanical cues by altering gene regulation in a feedback mechanism. Numerous mutations in A-type lamins cause a plethora of diverse diseases collectively termed as laminopathies, the majority of which are characterized by irregularly shaped, fragile, and plastic nuclei. These nuclei are challenged to normal mechanotransduction and lead to disease phenotypes. Here, we review our current understanding of the nucleocytoskeleton coupling in mechanotransduction mediated by lamins...
October 14, 2016: Cells
Alberto Avolio
Blood vessels function as conduits for distribution of blood throughout the circulatory system. Large arteries, in addition to the essential conduit function, also serve to dampen the effect of pulsatile ventricular ejection that generates pulsatile pressure with each cardiac cycle; that is, they exhibit a 'cushion' function. The conduit function can be compromised by intimal effects that cause obstruction to flow, generally attributed to plaque formation due to intimal changes affected by atherosclerotic processes...
September 2016: Journal of Hypertension
Jun Qiu, Fang-Fang Li
Mechanical properties of a single cell and its mechanical response under stimulation play an important role in regulating interactions between cell and extracellular matrix and affecting mechanotransduction. Osteocytes exhibit solid-like viscoelastic behavior in response to the interstitial fluid shear resulting from tissue matrix deformation. This study intends to quantitatively describe the mechanical behavior of osteocytes combining in vitro experiment and fluid-structure interaction (FSI) finite element (FE) model...
October 17, 2016: Biomechanics and Modeling in Mechanobiology
Jason Wu, Amanda H Lewis, Jörg Grandl
In 2010, two proteins, Piezo1 and Piezo2, were identified as the long-sought molecular carriers of an excitatory mechanically activated current found in many cells. This discovery has opened the floodgates for studying a vast number of mechanotransduction processes. Over the past 6 years, groundbreaking research has identified Piezos as ion channels that sense light touch, proprioception, and vascular blood flow, ruled out roles for Piezos in several other mechanotransduction processes, and revealed the basic structural and functional properties of the channel...
October 12, 2016: Trends in Biochemical Sciences
Hannah E Majeski, Jing Yang
Past decades of cancer research have mainly focused on the role of various extracellular and intracellular biochemical signals on cancer progression and metastasis. Recent studies suggest an important role of mechanical forces in regulating cellular behaviors. This review first provides an overview of the mechanobiology research field. Then we specially focus on mechanotransduction pathways in cancer progression and describe in detail the key signaling components of such mechanotransduction pathways and ECM components that are altered in cancer...
October 14, 2016: Molecular Pharmacology
Aaron P Russell, Marita A Wallace, Ming Kalanon, Evelyn Zacharewicz, Paul A Della Gatta, Andrew Garnham, Séverine Lamon
AIM: The striated muscle activator of Rho signalling (STARS) is a muscle-specific actin-binding protein. The STARS signalling pathway is activated by resistance exercise and is anticipated to play a role in signal mechanotransduction. Animal studies have reported a negative regulation of STARS signalling with age, but such regulation has not been investigated in humans. METHODS: Ten young (18-30 years) and 10 older (60-75 years) subjects completed an acute bout of resistance exercise...
October 14, 2016: Acta Physiologica
Philipp Niethammer
Forces deriving from blood flow shear modulate vascular adherence and transendothelial migration of leukocytes into inflamed tissues, but the mechanisms by which shear is sensed are unclear. In this issue, Fine et al. (2016. J. Cell Biol. identify the guanosine nucleotide exchange factor GEF-H1 as critical for shear stress-induced transendothelial neutrophil migration.
October 10, 2016: Journal of Cell Biology
Aidan P Maartens, Jutta Wellmann, Emma Wictome, Benjamin Klapholz, Hannah Green, Nicholas H Brown
Vinculin is a highly conserved protein involved in cell adhesion and mechanotransduction, and both gain and loss of its activity causes defective cell behaviour. Here, we examine how altering vinculin activity perturbs integrin function within the context of Drosophila development. Whereas loss of vinculin produced relatively minor phenotypes, gain of vinculin activity, via a loss of head-tail autoinhibition, caused lethality. The minimal domain capable of inducing lethality is the talin-binding D1 domain, and this appears to require talin-binding activity, as lethality was suppressed by competition with single vinculin binding sites from talin...
October 13, 2016: Journal of Cell Science
C Wilson, M Lee, J G McCarron
Circulating blood generates frictional forces (shear-stress) on the walls of blood vessels. These frictional forces critically regulate vascular function. The endothelium senses these frictional forces and, in response, releases various vasodilators that relax smooth muscle cells in a process termed flow-mediated dilatation. Whilst some elements of the signalling mechanisms have been identified, precisely how flow is sensed and transduced to cause the release of relaxing factors is poorly understood. By imaging signalling in large areas of the endothelium of intact arteries, we show that the endothelium responds to flow by releasing acetylcholine...
October 12, 2016: Journal of Physiology
Daniel Dziob, Tomasz Kołodziej, Justyna Nowak, Piotr Cyzio, Joanna Raczkowska, Jadwiga Laska, Zenon Rajfur
Cell migration is an important biological phenomenon which depends on a number of internal and external factors. One of such factors can be the mechanical properties of the environment which can have an impact on the cell's regulatory pathways through so-called mechanotransduction. Ultimately, these properties can also influence the process of cell migration. The goal of this work is to investigate how substrate stiffness (elasticity) changes basic migration parameters of migrating cells. Fish keratocytes migrating on polyacrylamide hydrogels have been used as a model of fast migrating cells...
October 11, 2016: Physical Biology
Arianna Mauretti, Noortje A M Bax, Mieke H van Marion, Marie José Goumans, Cecilia Sahlgren, Carlijn V C Bouten
For emerging cardiac regeneration strategies, it is essential to know if and how cardiac stem cells sense and respond to the mechanical stimuli provided by their environment in the beating heart. Here, we study the response to cyclic strain of undifferentiated and predifferentiated human cardiomyocyte progenitor cells (CMPCs), as well as the formation and activation of the cellular structures involved in mechanosensing, that we termed 'mechanosome'. Once verified that the applied uniaxial cyclic strain (10%, 0...
September 12, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Zhenhai Li, Hyunjung Lee, Cheng Zhu
Cell-matrix adhesion complexes are multi-protein structures linking the extracellular matrix (ECM) to the cytoskeleton. They are essential to both cell motility and function by bidirectionally sensing and transmitting mechanical and biochemical stimulations. Several types of cell-matrix adhesions have been identified and they share many key molecular components, such as integrins and actin-integrin linkers. Mechanochemical coupling between ECM molecules and the actin cytoskeleton has been observed from the single cell to the single molecule level and from immune cells to neuronal cells...
October 6, 2016: Experimental Cell Research
Mayumi Takeya, Yuushi Okumura, Takeshi Nikawa
Skin can respond to various types of internal and/or external mechanostimuli, such as excessive tension caused by body growth or decompression due to weight loss, which significantly affect skin morphology. Mechanosensors, including p130Cas, are reported to play a role in deformation and subsequent recovery of various tissues including skeletal muscles and blood vessels. However, the role of mechanotransduction via p130Cas in the regulation of skin size remains unclear. In this report, p130Cas activation was manipulated using a fibroblast-embedded collagen gel model or mouse skin contraction model...
October 7, 2016: Journal of Physiological Sciences: JPS
Theodoros Vassilakopoulos, Dimitrios Toumpanakis
In obstructive lung diseases, airway inflammation leads to bronchospasm and thus resistive breathing, especially during exacerbations. This commentary discusses experimental evidence that resistive breathing per se (the mechanical stimulus) in the absence of underlying airway inflammation leads to lung injury and inflammation (mechanotransduction). The potential implications of resistive breathing-induced mechanotrasduction in COPD exacerbations are presented along with the available clinical evidence.
2016: International Journal of Chronic Obstructive Pulmonary Disease
Guillermo García-Cardeña, Bendix R Slegtenhorst
Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system. From the onset of blood flow, the embryonic vasculature is continuously exposed to a variety of hemodynamic forces. These biomechanical stimuli are key determinants of vascular cell specification and remodeling and the establishment of vascular homeostasis. In recent years, major advances have been made in our understanding of mechano-activated signaling networks that control both spatiotemporal and structural aspects of vascular development...
October 6, 2016: Annual Review of Cell and Developmental Biology
Qiang He, Zhanwei Jia, Ying Zhang, Xiumin Ren
We aimed to investigate the effect of morin hydrate on neural stem cells (NSCs) isolated from mouse inner ear and its potential in protecting neuronal hearing loss. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and bromodeoxyuridine incorporation assays were employed to assess the effect of morin hydrate on the viability and proliferation of in vitro NSC culture. The NSCs were then differentiated into neurons, in which neurosphere formation and differentiation were evaluated, followed by neurite outgrowth and neural excitability measurements in the subsequent in vitro neuronal network...
October 6, 2016: Journal of Cellular and Molecular Medicine
Georgia Dalagiorgou, Christina Piperi, Christos Adamopoulos, Urania Georgopoulou, Antonios N Gargalionis, Anastasia Spyropoulou, Ilianna Zoi, Marjan Nokhbehsaim, Anna Damanaki, James Deschner, Efthimia K Basdra, Athanasios G Papavassiliou
Polycystin-1 (PC1) has been proposed as a chief mechanosensing molecule implicated in skeletogenesis and bone remodeling. Mechanotransduction via PC1 involves proteolytic cleavage of its cytoplasmic tail (CT) and interaction with intracellular pathways and transcription factors to regulate cell function. Here we demonstrate the interaction of PC1-CT with JAK2/STAT3 signaling axis in mechanically stimulated human osteoblastic cells, leading to transcriptional induction of Runx2 gene, a master regulator of osteoblastic differentiation...
October 3, 2016: Cellular and Molecular Life Sciences: CMLS
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