TY - JOUR. T1 - Global architecture of the F-actin cytoskeleton regulates cell shape-dependent endothelial mechanotransduction. AU - Shao, Yue. AU - Mann, Jennifer M.. AU - Chen, Weiqiang. AU - Fu, Jianping. PY - 2014/3. Y1 - 2014/3. N2 - Uniaxial stretch is an important biophysical regulator of cell morphology (or shape) and functions of vascular endothelial cells (ECs). However, it is unclear whether and how cell shape can independently regulate EC mechanotransductive properties under uniaxial stretch. Herein, utilizing a novel uniaxial cell-stretching device integrated with micropost force sensors, we reported the first experimental evidence showing cell shape-dependent EC mechanotransduction via cytoskeleton (CSK) contractile forces in response to uniaxial stretch. Combining experiments and theoretical modeling from first principles, we showed that it was the global architecture of the F-actin CSK that instructed the cell shape-dependent EC mechanotransductive process. Furthermore, a cell ...
Atherosclerosis is a focal disease that develops preferentially where nonlaminar, disturbed blood flow occurs, such as branches, bifurcations, and curvatures of large arteries. Endothelial cells sense and respond differently to disturbed flow compared with steady laminar flow. Disturbed flow that occurs in so-called atheroprone areas activates proinflammatory and apoptotic signaling, and this results in endothelial dysfunction and leads to subsequent development of atherosclerosis. In contrast, steady laminar flow as atheroprotective flow promotes expression of many anti-inflammatory genes, such as Kruppel-like factor 2 and endothelial nitric oxide synthase and inhibits endothelial inflammation and athrogenesis. Here we will discuss that disturbed flow and steady laminar flow induce pro- and antiatherogenic events via flow type-specific mechanotransduction pathways. We will focus on 5 mechanosensitive pathways: mitogen-activated protein kinases/extracellular signal-regulated kinase ...
Discovery may accelerate advances in understanding and treating hearing loss. National Institutes of Health-funded researchers have identified two proteins that may be the key components of the long-sought after mechanotransduction channel in the inner ear-the place where the mechanical stimulation of sound waves is transformed into electrical signals that the brain recognizes as sound. The findings are published in the Nov. 21 online issue of The Journal of Clinical Investigation.. The study used mice in which two genes, TMC1 and TMC2, have been deleted. The researchers revealed a specific functional deficit in the mechanotransduction channels of the mices stereocilia (bristly projections that perch atop the sensory cells of the inner ear, called hair cells), while the rest of the hair cells structure and function was normal.. These genes and the proteins they regulate are the strongest candidates yet in a decades-long search for the transduction channel that is at the center of the inner ...
TY - CHAP. T1 - Role of the plasma membrane in endothelial cell mechanosensation of shear stress. AU - Butler, Peter J.. AU - Chien, Shu. PY - 2013/1/1. Y1 - 2013/1/1. N2 - Mechanotransduction, which is the process by which cells convert mechanical stimuli to biochemical signaling cascades, is involved in the homeostasis of numerous tissues (reviewed in [21] and [56]). The mechanotransduction of hemodynamic shear stress by endothelial cells (ECs) has garnered special attention because of its role in regulating vascular health and disease. In particular, there is intense interest in identifying the primary molecular mechanisms of the EC sensing of shear stress because its (or their) discovery may lead to clinical interventions in atherosclerosis and other diseases related to mechanobiology. In this chapter, we address the hypothesis that the plasma membrane lipid bilayer is one endothelial cell mechanosensor. Here we define mechanosensor as a cellular structure that responds to mechanical ...
Mechanosensitive channels play important roles in the physiology of many organisms, and their dysfunction can affect cell survival. This suggests that they might be therapeutic targets in pathogenic organisms. Pathogenic protozoa lead to diseases such as malaria, dysentery, leishmaniasis and trypanosomiasis that are responsible for millions of deaths each year worldwide. We analyzed the genomes of pathogenic protozoa and show the existence within them of genes encoding putative homologues of mechanosensitive channels. Entamoeba histolytica, Leishmania spp., Trypanosoma cruzi and Trichomonas vaginalis have genes encoding homologues of Piezo channels, while most pathogenic protozoa have genes encoding homologues of mechanosensitive small-conductance (MscS) and K+-dependent (MscK) channels. In contrast, all parasites examined lack genes encoding mechanosensitive large-conductance (MscL), mini-conductance (MscM) and degenerin/epithelial Na+ (DEG/ENaC) channels. Multiple sequence alignments of evolutionarily
Mechanobiology : An emerging field at the interface of biology and engineering, mechanobiology explores the mechanisms by which cells sense and respond to mechanical signals-and holds great promise in one day unravelling the mysteries of cellular and extracellular matrix mechanics to cure a broad range of diseases. Mechanobiology: Exploitation for Medical Benefit presents a comprehensive overview of principles of
Cells are constantly adjusting to the mechanical properties of their surroundings, operating a complex mechanochemical feedback, which hinges on mechanotransduction mechanisms. Whereas adhesion structures have been shown to play a central role in mechanotransduction, it now emerges that the nucleus may act as a mechanosensitive structure. Here, we review recent advances demonstrating that mechanical stress emanating from the cytoskeleton can activate pathways in the nucleus which eventually impact both its structure and the transcriptional machinery.
TY - JOUR. T1 - Fishing for key players in mechanotransduction. AU - Nicolson, Teresa. PY - 2005/3. Y1 - 2005/3. N2 - The senses of touch and hearing involve transduction of mechanical stimuli into electrical signals. The search for components of the transduction apparatus in mechanosensory neurons has benefited greatly from genetic approaches using both invertebrates and vertebrates. A consensus model has emerged that includes extracellular and intracellular structural components arranged around a central mechanically gated channel. In the sensory hair cell of the inner ear, the extracellular structural component thought to have a key role in opening the transduction channel is the tip link. Although elusive for decades, recent studies have yielded candidates for both the transduction channel and the tip link in hair cells.. AB - The senses of touch and hearing involve transduction of mechanical stimuli into electrical signals. The search for components of the transduction apparatus in ...
Mechanotransduction is of fundamental importance in cell physiology, facilitating sensing in touch and hearing as well as tissue development and wound healing. This study used an impedance sensor to monitor the effective resistance and permittivity of artificial tissues, alginate hydrogel with encapsulated fibroblasts, which were kept viable through the use of a bespoke microfluidic system. The observed transient impedance responses upon the application of identical compressive normal loads differed between acellular hydrogels and hydrogels in which fibroblasts were encapsulated. These differences resulted from changes in the conductivity and permeability of the hydrogel due to the presence of the encapsulated fibroblasts, and transient changes in ion concentrations due to mechanotransduction effects.. ...
Nature Reviews Molecular and Cell Biology presents a special Focus on mechanotransduction - on a range of topics from how cells sense mechanical forces in different tissues to how these mechanical forces are transduced into biochemical signals - in development, normal physiology and disease. Cells sense their physical three-dimensional environment - properties of the extracellular matrix, neighbouring cells and physical stress - by translating mechanical forces and deformations into biochemical signals. In turn, these signals can adjust cellular and extracellular structure. This mechanosensitive feedback modulates cellular functions as diverse as proliferation, differentiation, migration and apoptosis, and is crucial for organ development and homeostasis. Any molecular defect that interrupts or alters this chain of mechanical sensing and subsequent cell signalling events could perturb the normal cellular function and potentially lead to diverse diseases such as loss of hearing, cardiovascular ...
Flow in the arterial system is mostly laminar, but turbulence occurs in vivo under both normal and pathological conditions. Turbulent and laminar flow elicit significantly different responses in endothelial cells (ECs), but the mechanisms allowing ECs to distinguish between these different flow regimes remain unknown. The authors present a computational model that describes the effect of turbulence on mechanical force transmission within ECs. Because turbulent flow is inherently noisy with random fluctuations in pressure and velocity, our model focuses on the effect of signal noise (a stochastically changing force) on the deformation of intracellular transduction sites including the nucleus, cell-cell adhesion proteins (CCAPs), and focal adhesion sites (FAS). The authors represent these components of the mechanical signaling pathway as linear viscoelastic structures (Kelvin bodies) connected to the cell surface via cytoskeletal elements. The authors demonstrate that FAS are more sensitive to signal
Martin Schwartz earned a BA in chemistry from New College in Sarasota FL and a PhD in physical chemistry from Stanford, where he worked in Harden McConnells lab on biophysics of phospholipid membranes.He then did postdoctoral research in biology at MIT in the laboratory of Richard Hynes where he studied interactions of fibronectin with cells and other proteins. He was on the faculty at Harvard Medical School, Scripps Research Institute and the University of Virginia prior to moving to Yale in 2011. Starting in the 1980s, his lab was among the first to report that integrin mediated adhesion could regulate signaling pathways in cells;that integrin-mediated adhesion promotes cell survival, that integrins synergize with growth factor receptors to activate growth signaling pathways and that integrins regulate Rho family GTPases. His lab has also elucidated mechanotransduction pathways by which endothelial cells respond to fluid shear stress to activate inflammatory pathways linked to ...
Martin Schwartz earned a BA in chemistry from New College in Sarasota FL and a PhD in physical chemistry from Stanford, where he worked in Harden McConnells lab on biophysics of phospholipid membranes.He then did postdoctoral research in biology at MIT in the laboratory of Richard Hynes where he studied interactions of fibronectin with cells and other proteins. He was on the faculty at Harvard Medical School, Scripps Research Institute and the University of Virginia prior to moving to Yale in 2011. Starting in the 1980s, his lab was among the first to report that integrin mediated adhesion could regulate signaling pathways in cells;that integrin-mediated adhesion promotes cell survival, that integrins synergize with growth factor receptors to activate growth signaling pathways and that integrins regulate Rho family GTPases. His lab has also elucidated mechanotransduction pathways by which endothelial cells respond to fluid shear stress to activate inflammatory pathways linked to ...
Considerable evidence exists to support the hypothesis that mechanical forces have an essential role in healthy embryonic skeletal development. Clinical observations and experimental data indicate the importance of muscle contractions for limb development. However, the influence of these forces is seldom referred to in biological descriptions of bone development, and perhaps this is due to the fact that the hypothesis that mechanical forces are essential for normal embryonic skeletal development is difficult to test and elaborate experimentally in vivo, particularly in humans. Computational modeling has the potential to address this issue by simulating embryonic growth under a range of loading conditions but the potential of such models has yet to be fully exploited. In this article, we review the literature on mechanobiology of limb development in three main sections: (a) experimental alteration of the mechanical environment, (b) mechanical properties of embryonic tissues, and (c) the use of ...
ABSTRACT Vascular endothelial cells (ECs) form a semiselective barrier for macromolecules and cell elements regulated by dynamic interactions between cytoskeletal elements and cell adhesion complexes
Cells use force sensors to detect and distinguish between many of the physical signals that they experience.. A major class of force sensors are mechanosensitive ion channels. These are holes, or pores, in the surface of the cell that can open and shut.. When the cell senses a physical force or a mechanical stimulus (in essence, like a microscopic prod), these pores can open. Chemicals move in and out, and a tiny electrical current is conducted across the cell wall. This can be measured by attaching small electrodes to the surface of a cell.. Many types of cells and tissues have such sensors, and respond to changes in mechanical loads. These include the neurons that underpin our sense of touch, metastasising cancer cells and the cells that maintain our cartilage in bones.. The drug EVENITY - which aims to prevent bone loss in osteoporosis - acts through this pathway. The drug blocks sclerostin, a key factor that naturally inhibits bone formation based on the mechanosensing functions of ...
Mechanotransduction - from how cells sense mechanical forces in different tissues to how these mechanical forces are transduced into biochemical signals - is an essential biological process in development, normal physiology and disease. In this exciting area, we are particularly interested in investigating the role of mechano-biological processes associated with cell-cell and cell-matrix adhesions (e.g. topography and rigidity of the extracellular matrix) in the regulation of collective and directed cell migration and tissue morphogenesis. Using a combination of various techniques, from molecular biology to nanotechnology and live cell imaging, for example, we have been accumulating interesting data suggesting that one of the most important factors distinguishing metastatic from non-metastatic cells could be their ability to collectively invade and migrate towards blood vessels by physically interacting with the surrounding extracellular matrices. By experimenting with the ...
Mechanotransduction - from how cells sense mechanical forces in different tissues to how these mechanical forces are transduced into biochemical signals - is an essential biological process in development, normal physiology and disease. In this exciting area, we are particularly interested in investigating the role of mechano-biological processes associated with cell-cell and cell-matrix adhesions (e.g. topography and rigidity of the extracellular matrix) in the regulation of collective and directed cell migration and tissue morphogenesis. Using a combination of various techniques, from molecular biology to nanotechnology and live cell imaging, for example, we have been accumulating interesting data suggesting that one of the most important factors distinguishing metastatic from non-metastatic cells could be their ability to collectively invade and migrate towards blood vessels by physically interacting with the surrounding extracellular matrices. By experimenting with the ...
Tissue injury disrupts the mechanical homeostasis that underlies normal tissue architecture and function. The failure to resolve injury and restore homeostasis gives rise to progressive fibrosis that is accompanied by persistent alterations in the mechanical environment as a consequence of pathological matrix deposition and stiffening. This Review focuses on our rapidly growing understanding of the molecular mechanisms linking the altered mechanical environment in injury, repair, and fibrosis to cellular activation. In particular, our focus is on the mechanisms by which cells transduce mechanical signals, leading to transcriptional and epigenetic responses that underlie both transient and persistent alterations in cell state that contribute to fibrosis. Translation of these mechanobiological insights may enable new approaches to promote tissue repair and arrest or reverse fibrotic tissue remodeling.. ...
PI: Daniel Fletcher, Ph.D. NIH R01 application, PA-18-484 Project Title: Mechanical regulation of acting binding proteins Project Period: 07/01/2019 ? 06/30/202...
WUNDHEILUNG (MEDIZIN); ZELLWANDERUNG (CYTOLOGISCHE HISTOLOGIE); ZELLDIFFERENZIERUNG + ZELLREIFUNG (CYTOLOGIE); MECHANISCHE AKTIVITÄT DER ZELLE (CYTOLOGIE); WOUND HEALING (MEDICINE); CELL MIGRATION (CYTOLOGICAL HISTOLOGY); CELL DIFFERENTIATION + CELL MATURATION (CYTOLOGY); MECHANICAL ACTIVITY OF CELLS (CYTOLOGY ...
Page contains details about calcein-loaded mechanosensitive channel of large conductance proteoliposomes . It has composition images, properties, Characterization methods, synthesis, applications and reference articles : nano.nature.com
The central nervous system consists of two cell classes, neurons and glia. Mechanosensitive channels are expressed on the plasma membrane of both non-sensory neurons and glial cells. Different...
Cancer is initiated by genetic modifications, but develops by altering its own physical context. It is through a process known as mechanotransduction that cells sense their environment and adapt to it by modifying their own cellular as well as the extracellular structure. There is increasing appreciation that mechanical forces play a key role in many of the hallmarks of cancer. However, the cellular and extracellular changes by which tumor cells adapt to mechanical forces are often overlooked and therefore incompletely understood, as is the potential involvement of specific oncogenes.. A team of researchers from the Zernike Institute for Advanced Materials and the Cancer Research Center of the UMCG are committed to making a quantitative connection between physical forces and genetic defects. In order to identify the specific strengths of this team, in relation to activities elsewhere in the Netherlands, we have started with five seed projects. The aim of these projects is to study the stiffness ...
download molecular and was by Cardinal Eugenio Pacelli( community Pius XII) on ergodic of Pope Pius XI to the identidades of England providing the appraisal of Chesterton. Chesterton provided of interesting item Imprint on the man of 14 June 1936, at his paper in Beaconsfield, Buckinghamshire. His rich basic dynamics cried a download molecular and cellular mechanobiology changed to his recipient.
The Biophysical Society thematic meeting on the Mechanobiology of Disease aims to bring together an interdisciplinary set of researchers and...
the related terms mechanosensing, mechanosignaling, and mechanotransduction refer to the sensing of physical forces by cells and their translation into a biochemical response, analogous to the processes termed chemotransduction. Among the various physical forces to which cells in vivo are constantly exposed, mechanical stimuli associated with blood flow are particularly important. Indeed, fluid shear stress and distending pressure that act on the vessel wall play a major role in vascular homeostasis. The vascular endothelium, by virtue of its location, serves as an interface between the blood and tissue for hemodynamic changes. Recent work demonstrates that the endothelium senses and integrates hemodynamic stimuli including shear to effect maintenance of vascular function and possibly modulate the onset of vascular disease. The currently accepted paradigm is that sensing of a change (either increase or decrease) in the shear force occurs via elements on the endothelial cell membrane that ...
The responses of living cells to external mechanical and electrical stimulation play important roles in regulating their biological functions and behaviors, and the response mechanisms have attracted great attentions. Global stimulation on cells is generally used in traditional methods, but it is insufficien
Tumors are stiffer than normal tissue, and tumors have altered integrins. Because integrins are mechanotransducers that regulate cell fate, we asked whether tissue stiffness could promote malignant behavior by modulating integrins. We found that tumors are rigid because they have a stiff stroma and …
Increasing pressure caused an increased in the viability at 4h after the mechanical stimulation, and that was sustained for 24h. Those results were complemented with cell cycle analysis showing an increment in the cells in S-phase confirming the proliferative effect. We observed a pressure-dependent single-cell detachment pattern on both cell lines when compared to controls. This migratory pattern was studied the cell-cell and cell-substrate adhesions molecules (E-cadherin and ß-catenin, and ß1integrin, respectively) which revealed decreased. It seems an amoeboid migration variant of the single-cell migration pat-tern.Besides that, cells submitted to pressure presented an increase in stress fibers, a cortical actin pattern, lamelipodia and filopodia. ...
If you have a question about this talk, please contact Hannah Main.. Abstract not available. This talk is part of the Computational Biology Workshop 2017 series.. ...
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A hydraulic pump is a mechanical device that converts mechanical power into hydraulic energy. It generates flow with enough power to overcome pressure induced by the load.
Anatomy of the ear shows three parts : external, middle and internal. The organs of hearing and equilibrium convert mechanical energy to receptor (action) potential.
Zhong Lin Wang, a Regents professor in the School of Materials Science and Engineering at the Georgia Institute of Technology leads a team that has developed a self-charging power cell that directly converts mechanical energy to chemical energy, storing the power until it is released as electrical current. The technology eliminates the need to convert ...
Electric generator: Electric generator, any machine that converts mechanical energy to electricity for transmission and distribution over power lines to domestic, commercial, and industrial
Although the changes in interchain contacts during opening and closing are of interest, the available models have modest resolution (3.5-3.7 Å) that is insufficient for sidechain positions to be known accurately. In addition, each of the seven chains in 2oau was apparently solved independently: when chains B-G are aligned[13], one at a time, with chain A, the median RMS deviation for alpha carbons is 1.54 Å (range 0.57-1.84). This could lead to variations in interchain contacts that may not be meaningful. The seven chains in 2vv5 were apparently restrained to similar conformations: the median alpha carbon RMS (between chain A and the other six) is only 0.07 Å (range 0.10 - 0.09 Å; sidechain RMS runs about 0.4 Å). Chains B-G aligned to chain A for 2oau ...
A method and apparatus for providing high bandwidth and low noise mechanical input and output for computer systems. A gimbal mechanism provides two revolute degrees of freedom to an object about two axes of rotation. A linear axis member is coupled to the gimbal mechanism at the intersection of the two axes of rotation. The linear axis member is capable of being translated along a third axis to provide a third degree of freedom. The user object is coupled to the linear axis member and is thus translatable along the third axis so that the object can be moved along all three degrees of freedom. Transducers associated with the provided degrees of freedom include sensors and actuators and provide an electromechanical interface between the object and a digital processing system. Capstan drive mechanisms transmit forces between the transducers and the object. The linear axis member can also be rotated about its lengthwise axis to provide a fourth degree of freedom, and, optionally, a floating gimbal mechanism
McKay Laboratorys mission is to conduct high quality fundamental and translational research and to train the next generation of leaders in the orthopaedic field.
Cells will ramp up gene expression in response to physical forces alone, a new study finds. Gene activation, the first step of protein production, starts less than one millisecond after a cell is stretched-hundreds of times faster than chemical signals can travel, the researchers report.
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Our research lies at the interface of vascular inflammation and endothelial mechanobiology, and addresses the mechanisms of endothelial vulnerability leading to atherosclerosis. We apply a multidisciplinary systems approach, and develop novel technologies and protocols to test how arterial hemodynamics locally regulates inflammation induced by systemic risk factors for vascular disease to affect lesion formation. The outcomes of this work will be the elucidation of a vulnerable endothelial phenotype and a better understanding of mechanisms to guide the development of novel strategies to prevent, diagnose and treat cardiovascular disease.. ...
Water is the solvent in which most physical, chemical and biological processes take place. Therefore, it is essential to understand the nature of interactions between molecules dissolved in water in order to understand many of these processes. Two of the most important of these processes are the adherence of substances to cell membranes and the withdrawal of proteins. Both of these are fundamental in biomedical research, since a substantial part of the process of designing new drugs is based on understanding how substances penetrate cell membranes to enter cells. These drugs are often proteins designed to prevent or strengthen the action of other substances. In these cases, accurately identifying the protein folding is essential, since the form these proteins take on when they fold influences how effectively they are able to act ...
This course will cover the biochemical signaling in response to various mechanical stresses in the context of physiology and pathophysiology. Topics include the behavior of live cells during cell motility, force generation, and interaction with the extracellular matrix; the advanced biomechanical testing tools used for in vitro characterization of living cells; mechanotransduction that converts mechanical forces into biochemical signaling. ...
Here, we report a mechanotransduction pathway in osteocytes that links FSS to the activation of Ca2+ influx that drives the mechanically induced suppression of sclerostin abundance. Central to our discovery was that the MT network, and more specifically the abundance of detyrosinated tubulin that defined the cytoskeletal stiffness, determined the mechanosensitivity of osteocytes to FSS. Upon a threshold amount of FSS, MT-dependent activation of NOX2 elicited ROS that activated TRPV4-dependent Ca2+ influx signals and CaMKII phosphorylation, driving sclerostin down-regulation in osteocytes (Fig. 8E). Our data revealed new molecular players and provided insights into osteocyte mechanotransduction.. Our data showed that MTs are required for mechanosignaling, consistent with reports on other mechanosignaling events in the bone (31-34). We build upon this concept by demonstrating that the MT network, and specifically its abundance of detyrosinated tubulin, was a critical regulator of cytoskeletal ...
A common concern regarding the use of Xenopus oocytes for the heterologous expression of ion channels is the presence of endogenous channels, which may complicate single-channel studies by providing unwanted background signal (Sobczak et al., 2010; Terhag et al., 2010). An important consideration for our studies was potential interference by endogenous mechanosensitive channels, which have been reported in both excised and cell-attached patches of Xenopus ootyes (Methfessel et al., 1986; Taglietti and Toselli, 1988; Yang and Sachs, 1990; Lane et al., 1991). However, as shown in Fig. 1 B, although endogenous mechanosensitive channels are frequently present in cell-attached patches, they are not active in excised patches under our conditions. Although we cannot completely rule out a minor effect of endogenous channels on our recordings, their contribution to the final conductance measured under tension appears negligible; in traces at relatively high tensions, with all MscS single-channel events ...
An emerging field at the interface of biology and engineering, mechanobiology explores the mechanisms by which cells sense and respond to mechanical signals-and holds great promise in one day unravelling the mysteries of cellular and extracellular matrix mechanics to cure a broad range of diseases. Mechanobiology: Exploitation for Medical Benefit presents a comprehensive overview of principles of mechanobiology, highlighting the extent to which biological tissues are exposed to the mechanical environment, demonstrating the importance of the mechanical environment in living systems, and critically reviewing the latest experimental procedures in this emerging field.. Featuring contributions from several top experts in the field, chapters begin with an introduction to fundamental mechanobiological principles; and then proceed to explore the relationship of this extensive force in nature to tissues of musculoskeletal systems, heart and lung vasculature, the kidney glomerulus, and cutaneous tissues. ...
Altered fluid flow, which is found in branches and curvatures of arteries, results in abnormal forces on the endothelial cells (EC). These forces have been shown to alter EC gene expression and phenotype and to activate several cellular structures including G-proteins, ion channels, adhesion molecules, and caveolae. Recently, PECAM-1 has been implicated as the primary sensor of hemodynamic forces in EC. Shear stress rapidly induces tyrosine phosphorylation of PECAM-1 and the recruitment of SHP-2. These events appear to contribute to shear-activation of ERK1/2. Additionally, PECAM-1 has been shown to form a mechanosensory signaling complex with VE-cadherin, VEGFR2, and βcatenin which plays a role in adhesion molecule expression and regulation of NF-κB. Past work has shown that caveolae membrane domains also serve as mechanotransduction sites that regulate many of these same second messengers. Based on these novel observations, we hypothesize that the PECAM-1 mediated mechanotransduction ...
TY - JOUR. T1 - Mechanotransduction in vivo by repeated talin stretch-relaxation events depends upon vinculin. AU - Margadant, Felix. AU - Chew, Li Li. AU - Hu, Xian. AU - Yu, Hanry. AU - Bate, Neil. AU - Zhang, Xian. AU - Sheetz, Michael. PY - 2011/12/1. Y1 - 2011/12/1. N2 - Mechanotransduction is a critical function for cells, in terms of cell viability, shaping of tissues, and cellular behavior. In vitro, cellular level forces can stretch adhesion proteins that link extracellular matrix to the actin cytoskeleton exposing hidden binding sites. However, there is no evidence that in vivo forces produce significant in vivo stretching to cause domain unfolding. We now report that the adhesion protein, talin, is repeatedly stretched by 100-350 nm in vivo by myosin contraction of actin filaments. Using a functional EGFP-N-Talin1-C-mCherry to measure the length of single talin molecules, we observed that the C-terminal mCherry was normally displaced in the direction of actin flow by 90 to ,250 nm ...
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Podocytes are specialized, highly differentiated epithelial cells in the kidney glomerulus that are exposed to glomerular capillary pressure and possible increases in mechanical load. The proteins sensing mechanical forces in podocytes are unconfirmed, but the classic transient receptor potential ch …
Guasch J, Diemer J, Riahinezhad H, Neubauer S, Kessler H, Spatz JP (2016). Synthesis of binary nanopatterns on hydrogels for initiating cellular responses. Chemistry of Materials 28:1806-1815. Guasch J, Conings B, Neubauer S, Rechenmacher F, Ende K, Rolli CG, Kappel C, Schaufler V, Micoulet A, Kessler H, Boyen H-G, Cavalcanti-Adam EA, Spatz JP (2015). Segregation versus colocalization: Orthogonally functionalized binary micropatterned substrates regulate the molecular distribution in focal adhesions. Advanced Materials 27:3737-3747. Frohnmayer JP, Brüggemann D, Eberhard C, Neubauer S, Mollenhauer C, Boehm H, Kessler H, Geiger B, Spatz JP (2015). Minimal synthetic cells to study integrin-mediated adhesion. Ang Chemie Int Ed. 54:12472-12478. Das T, Safferling K, Rausch S, Grabe N, Boehm H, Spatz JP (2015). A molecular mechanotransduction pathway regulates collective migration of epithelial cells. Nat Cell Biol. 17:76-87. Janiesch JW, Weiss M, Kannenberg G, Hannabuss J, Surrey T, Platzman I, Spatz ...
Mechanical forces play an increasingly recognized role in modulating cell function. This report demonstrates mechanosensing by T cells, using polyacrylamide gels presenting ligands to CD3 and CD28. Naive CD4 T cells exhibited stronger activation, as measured by attachment and secretion of IL-2, with increasing substrate elastic modulus over the range of 10-200 kPa. By presenting these ligands on different surfaces, this report further demonstrates that mechanosensing is more strongly associated with CD3 rather than CD28 signaling. Finally, phospho-specific staining for Zap70 and Src family kinase proteins suggests that sensing of substrate rigidity occurs at least in part by processes downstream of T-cell receptor activation. The ability of T cells to quantitatively respond to substrate rigidly provides an intriguing new model for mechanobiology. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.
TY - JOUR. T1 - Shear stress activation of SREBP1 in endothelial cells is mediated by integrins. AU - Liu, Yi. AU - Chen, Benjamin P C. AU - Lu, Min. AU - Zhu, Yi. AU - Stemerman, Michael B.. AU - Chien, Shu. AU - Shyy, John Y J. PY - 2002/1/29. Y1 - 2002/1/29. N2 - We investigated the effect of shear stress on the sterol regulatory element-binding protein 1 (SREBP1) in vascular endothelial cells (ECs) and the mechanotransduction mechanism involved. Application of a shear stress (12 dyn/cm2) caused the proteolytic cleavage of SREBP1 and the ensuing translocation of its transcription factor domain into the nucleus. As a result, shear stress increased the mRNAs encoding the low density lipoprotein receptor (LDLR), as well as the binding of 125I-LDL. Using a step flow channel, we showed that SREBP1 activation in ECs under laminar flow is transient, but disturbed flow causes sustained activation. In studying the shear stress-elicited molecular signaling that activates SREBP1, we found that blocking ...
Most cells are known to respond to mechanical cues, which initiate biochemical signalling pathways and play a role in cell membrane electrodynamics. These cues can be transduced either via direct activation of mechanosensitive (MS) ion channels or through deformation of the cell membrane and cytoskeleton. Investigation of the function and role of these ion channels is a fertile area of research and studies aimed at characterizing and understanding the mechanoactive regions of these channels and how they interact with the cytoskeleton are fundamental to discovering the specific role that mechanical cues play in cells. In this review, we will focus on novel techniques, which use magnetic micro- and nanoparticles coupled to external applied magnetic fields for activating and investigating MS ion channels and cytoskeletal mechanics.
CiteSeerX - Scientific documents that cite the following paper: Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism.
J Suslak , T , Watson , S , Thompson , K J , Shenton , F C , Bewick , G S , Armstrong , J D & Jarman , A P 2015 , Piezo is essential for amiloride-sensitive stretch-activated mechanotransduction in larval Drosophila dorsal bipolar dendritic sensory neurons , PloS ONE , vol. 10 , no. 7 , 0130969 . https://doi.org/10.1371/journal.pone. ...
Recent developments in modeling the relationship between bone microstructure and mechanotransduction are reviewed. The focus is on the relationship between the bone microstructure and the mechanosensation mechanism by which osteocytes sense the bone fluid motion propelled by the mechanical loading of the whole bone.
National Institutes of Health-funded researchers have identified two proteins that may be the key components of the long-sought after mechanotransduction channel in the inner ear - the place where the mechanical stimulation of sound waves is transformed into electrical signals that the brain recognizes as sound.
This thesis describes the investigation of the mechanosensitive channel of small conductance (MscS). The Escherichia coli MscS structure shows a homoheptameric ion channel with each monomer consisting of 3 transmembrane (TM) helices leading into the cytoplasmic domain. TM3 from each of the 7 subunits form the pore that opens up into a cytoplasmic cage, thought to be a molecular sieve. In order to further knowledge regarding the mechanism behind bacterial mechanosensation, several approaches were employed. Homologs from organisms indigenous to environments with temperatures ranging from 30°C to 95°C were cloned, expressed, and characterized. Chimeras were constructed between MscS homologs from 6 hyperthermophilic organisms and E. coli MscS, exchanging the transmembrane and cytoplasmic domains. Each protein is engineered with an N-terminal His6 tag and a C-terminal FLAG epitope. 4 homologs were found to be cytotoxic while 3 chimeras failed to rescue the osmotic-shock sensitivity of an E. coli ...
To many animals, including humans, some of the best things in life are mechanical. Not only courtship and sex but also simple movements such as walking depend on the ability to transform mechanical energy in the form of touch, sound, and muscle tension into ionic currents. This ability is also essential for control of osmotic balance, bladder function, and blood pressure in mammals. To meet these diverse needs, animals bear numerous sensory organs that contain either ciliated or nonciliated mechanoreceptor cells. Vertebrate hair cells and insect chordotonal neurons are examples of ciliated mechanoreceptor cells; mechanoreceptive neurons that innervate the body surface of nematodes, insects, and mammals are examples of nonciliated mechanoreceptor cells. All of these cells share the ability to signal the presence of mechanical stimuli by opening ion channels. Mechanical energy may activate mechanotransduction channels directly or indirectly. Only now are we beginning to uncover proteins that are ...
Differential adhesion between cadherin subtypes expressed on cell surfaces is postulated to direct cell segregation during tissue morphogenesis. The studies described here used magnetic twisting cytometry and traction force microscopy to test the impact of cadherin binding selectivity on mechanotransduction and substrate rigidity sensing at cadherin-based adhesions. Micropipette measurements in turn quantified the binding affinities of different cadherin subtypes. Here we present evidence that …
Differential adhesion between cadherin subtypes expressed on cell surfaces is postulated to direct cell segregation during tissue morphogenesis. The studies described here used magnetic twisting cytometry and traction force microscopy to test the impact of cadherin binding selectivity on mechanotransduction and substrate rigidity sensing at cadherin-based adhesions. Micropipette measurements in turn quantified the binding affinities of different cadherin subtypes. Here we present evidence that …
Bioengineering approaches to map mechanotransduction in the living cell Abstract Mechanical forces strongly influence the growth and form of virtually every tis...
TY - JOUR. T1 - Mechanotransduction by integrin is essential for IL-6 secretion from endothelial cells in response to uniaxial continuous stretch. AU - Sasamoto, Akitoshi. AU - Nagino, Masato. AU - Kobayashi, Satoshi. AU - Naruse, Keiji. AU - Nimura, Yuji. AU - Sokabe, Masahiro. N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2005/5. Y1 - 2005/5. N2 - We previously reported that uniaxial continuous stretch in human umbilical vein endothelial cells (HUVECs) induced interleukin-6 (IL-6) secretion via IκB kinase (IKK)/nuclear factor-κB (NF-κB) activation. The aim of the present study was to clarify the upstream signaling mechanism responsible for this phenomenon. Stretch-induced IKK activation and IL-6 secretion were inhibited by application of α5β1 integrin-inhibitory peptide (GRGDNP), phosphatidylinositol 3-kinase inhibitor (LY-294002), phospholipase C-γ inhibitor (U-73122), or protein kinase C inhibitor (H7). Although depletion of intra- or extracellular Ca2+ pool ...
The neural basis of auditory motion generation is supported by the mechanics of the receiver in nompC2 mutants (24, 29). nompC encodes a mechanosensory transduction channel (29) that accounts for about half the compound electrical response of the mechanosensory neurons in the auditory system of the fly (15). In nompC2 mutants, the nonlinearity of the receiver was markedly reduced (Fig. 4A). When the stimulus particle velocity was decreased from 10−3 to 10−5 m/s, fR shifted down from 634 ± 30 Hz to 579 ± 20 Hz (Δ = 55 Hz) in the mutants and from 791 ± 26 Hz to 402 ± 11 Hz (Δ = 389 Hz) in controls (Fig. 4B). The slopes of the shift were 1.4 and 9.7 Hz/dB for mutants and controls, respectively (Fig. 4B). This partial linearization coincided with a reduced oscillation activity. In nompC2 mutants, the power of the spontaneous oscillations of the receiver was nearly 4 times less than in controls (Figs. 5 and 6). Instead of the single resonance observed in responses to sound, the spontaneous ...
TY - JOUR. T1 - Properties of the mechanosensitive channel MscS pore revealed by tryptophan scanning mutagenesis. AU - Rasmussen, Tim. AU - Rasmussen, Akiko. AU - Singh, Shivani. AU - Galbiati, Heloisa. AU - Edwards, Michelle D.. AU - Miller, Samantha. AU - Booth, Ian R.. N1 - Funding This work was supported by a Wellcome Trust Programme grant [092552/A/10/Z awarded to I.R.B., S.M., J. H. Naismith (University of St Andrews, St Andrews, U.K.), and S. J. Conway (University of Oxford, Oxford, U.K.)] (T.R. and M.D.E.), by a BBSRC grant (A.R.) [BB/H017917/1 awarded to I.R.B., J. H. Naismith, and O. Schiemann (University of St Andrews)], by a Leverhulme Emeritus Fellowship (EM-2012-060\2), and by a CEMI grant to I.R.B. from the California Institute of Technology. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013 FP7/2007-2011) under Grant PITN-GA-2011-289384 (FP7-PEOPLE-2011-ITN NICHE) (H.G.) (awarded to S.M.).. PY - ...
The PIEZO2 gene is located on the short arm of chromosome 18. It spans a length of 482 kb of DNA and its coding sequence is spread across 55 exons. The protein product encoded by this gene has a molecular mass of 318 kDa and consists of 2752 amino acids. Several additional isoforms of the PIEZO2 protein exist due to alternatively spliced transcript variants. The gene is found to be overexpressed in the brain, spinal cord, pancreas, liver and lung. Heterozygous mutations in the PIEZO2 gene, including missense variants and deletions, have been linked to the disorders of MWKS, DA3 and DA5. So far only one mutation (R2686C) has been identified in MWKS. Homozygous and compound heterozygous mutations in the gene associated with Distal Arthrogryposis, with Impaired Proprioception and Touch (DAIPT) mainly include nonsense variants and deletions that cause frameshift and premature truncation, often resulting in a non-functioning PIEZO2 protein.. ...
This report studies Global Optical Tweezers (Mechanobiology Equipment) Market 2017, especially in North America, China, Europe, Southeast Asia, Japan and...
The vision of the research group in COntinuum Biomechanics and Mechanobiology is on developing a systemic, comprehensive system models in health and disease. Our approach is to integrate experimental methods, mathematical modeling and numerical simulations. We utilize our expertise for various biomechanical applications and basic research projects.
The Section on Mechanobiology develops and utilizes advanced Atomic Force Microscopy technologies for cellular and tissue mechanics studies.
UCL Discovery is UCLs open access repository, showcasing and providing access to UCL research outputs from all UCL disciplines.
heparin-binding growth-associated molecule; osteoblastic cells; mechanical loading; mechanotransduction; signal transduction; PKC; PKA; MAPK; gene-expression; bone-cells; mc3t3-e1 osteoblasts; in-vivo; c-fos; strain; kinase; release; protein; ...
Nanion offers analysis instruments for ion channel analysis, as patch clamp, impedance and bilayer recordings, used for drug development as cardiac safety and basic research.
Clinical and experimental studies have highlighted that the human body continuously adapts in response to altering environmental factors, different lifestyles, aging, injuries, and diseases. To gain more insights into the causes and consequences of adaptation mechanisms in the cardiovascular system, one needs to understand better how stresses are distributed throughout the tissue and how cells can sense and convert mechanical forces into biochemical signals that ultimately modulate cell and tissue properties. In particular, this volume focuses on the biomechanical material modeling and simulation of phenomena at the nano, micro, and macro levels in fibrous soft tissues of the cardiovascular system. This includes the determination of more realistic stress distributions in healthy and aneurysmatic aortic walls, an analysis of the impact of the intracellular filament organization on the tissue remodeling rate, and a revised method to quantify shear deformations and corresponding stresses in planar ...
From embryogenesis, to osteoarthritis, to cancer, physical forces and mechanical properties of tissues play a key role in health and disease. Many physical models of tissues largely focus on a single level of complexity e.g. individual cells or large collections of cells. A multi-scale approach is critically needed to address the complex interplay of mechanisms at each level, and bridge the gap between models at different levels. My long-term goal is to use multi-scale modeling to explain how mechanical forces are sensed and transmitted from molecules to cells to tissues, and how these processes impact tissue dynamics, properties, and biological functions. To this end, my group uses a combination of analytical theory and computer simulations to investigate time-dependent mechanical properties of tissues based on interplay of mechanics, geometry, and statistical physics of underlying components. Our models are informed and tested via close collaborations with experimental labs.. ...
Topographical and mechanical properties of adhesive substrates provide important biological cues that affect cell spreading, migration, growth, and differentiation. The phenomenon has led to the increased use of topographically patterned and flexible substrates in studying cultured cells. However, these studies may be complicated by various limitations. For example, the effects of ligand distribution and porosity are affected by topographical features of 3D biological constructs. Similarly, many studies of mechanical cues are compounded with cellular deformation from external forces, or limited by comparative studies of separate cells on different substrates. Furthermore, understanding cell responses to mechanical input is dependent upon reliable measurements of mechanical properties. This work addresses each of these issues. To determine how substrate topography and focal adhesion kinase (FAK) affect cell shape and movement, I studied FAK-null (FAK -/-) and wild type mouse 3T3
Mechanosensitive ion channels (MS channels) represent a diverse population of ion channels. Other membrane-associated proteins with different biophysical properties apart from ion channels, specialized cytoskeletal proteins, cell junction molecules and G-protein-coupled receptors and kinases, among many others are also considered mechanosensitive. MS channels integrate a variety of mechanical stimuli such as shear stress, tension, torsion, and compression and translate them into short-term effects (i.e., changes in ion concentrations and voltage) and long-term effects via changes in gene expression.. ...
Mechanosensitive ion channels (MS channels) represent a diverse population of ion channels. Other membrane-associated proteins with different biophysical properties apart from ion channels, specialized cytoskeletal proteins, cell junction molecules and G-protein-coupled receptors and kinases, among many others are also considered mechanosensitive. MS channels integrate a variety of mechanical stimuli such as shear stress, tension, torsion, and compression and translate them into short-term effects (i.e., changes in ion concentrations and voltage) and long-term effects via changes in gene expression. ...
We are investigating how intercellular adhesion proteins sense and transmit mechanical signals between cells in tissues. Using precision force probes, we established that cadherin complexes, which are crucial cell-cell adhesion proteins are mechanosensors. We are investigating how force-induced conformational changes in proteins in this complex trigger molecular and signaling cascades that regulate cell functions in tissues and in engineered scaffolds. Using a systems level approach, we are also establishing how integrins and cadherins coordinate functions to regulate global cell properties and broader tissue mechanics. Our approach combines nanomechanical measurements and live cell imaging to follow dynamic force-actuated changes in cells. We are collaborating with Cara Gottardi and with J. de Rooij to identify key cellular components required for mechanosensing. In addition, we use single molecular AFM studies and molecular dynamics simulations to determine how forces alter protein ...
The transition from a reparative to a fibrotic response likely arises from a failure or inability to resolve and repair injury. While multiple explanations for this transition have been offered (17, 18), mechanical forces are likely instrumental. For instance, while changes in vascular permeability evolved to mitigate acute injuries and initiate protective and reparative processes, failure to resolve such acute responses in a timely fashion imposes persistent aberrant mechanical states that play important roles in propagating injury and pathological remodeling (4, 19). Similarly, in dermal wound healing, tissue repair ultimately decreases stresses in the wound bed, allowing activated myofibroblasts to undergo apoptosis or return to a more quiescent state (20, 21). In contrast, wound splinting, which prevents dermal contraction, or exposure to chronic mechanical stresses maintains myofibroblast activation, impedes healing, and enhances scar formation. Shielding the wound from stress with ...
Biomechanics involves the study of the interactions of physical forces with biological systems at all scales, including molecular, cellular, tissue, organ, and species levels. The emerging field of Mechanobiology focuses on how cells produce and respond to mechanical forces, bridging the science of mechanics with the disciplines of biophysics and molecular biology. The theme of this conference is the linking of disparate spatial and temporal scales using experimentation, image analysis, visualization, and computing to investigate problems in biological and medicine science and technology. Discussions will relate to state-of-the-art research in computational sciences which investigate phenomena in Biomechanics and Mechanobiology. Emphasis will be placed on novel techniques in computing, experimentation, visualization, and multidisciplinary research approaches that demonstrate successful synergies; computational reconstruction of experimental findings; and experimental and visualization techniques ...
Using a unique single-molecule force measurement tool, a research team has developed a clearer understanding of how platelets sense the mechanical forces they encounter during bleeding to initiate the cascading process that leads to blood clotting. Beyond providing a better understanding of this vi
Ageing is a central aspect of life itself. Even after extensive research during the last decades, little is known about this highly complex biological process. In conclusion, the achievement of scientific milestones such as an increased healthspan or the retaining of cognitive functions is still in distant future. Another aspect poorly understood in terms of biochemical signalling pathways is the communication via mechanical cues also termed mechanosensing and -transduction. Both aspects, neuronal ageing and mechanosensing in neuronal cells will be addressed and connected in this thesis. As central aspect, first we present an in vitro model optimised for long-term culturing conditions to define hallmarks of neuronal ageing in more detail. Known as one central hallmark of ageing from mammalian and human research, the focus of investigations was set on the control of proteostasis. With different experimental approaches such as immunocytochemistry, western blotting, FUNCAT and BONCAT, we showed ...
News & Opinion Telomere Length and Childhood Stress Dont Always Correlate Shorter telomere length is widely considered a manifestation of stress in young children, but the results of a new study find its more complicated than that. ...
The most common devices that can be qualified for voltage sources are alternators and batteries. Alternators convert mechanical energy into an AC output thanks to the phenomenon of electromagnetic induction. On the other hand, batteries provide a DC output from a chemical source of energy.. Ideally, whether we deal with a DC or AC device, a voltage source should provide a stable and constant output value regardless of the output load, and therefore current that must be provided. Ideal voltage sources are defined by a flat voltage/current characteristic which implies that an infinite amount of power could be provided to a load.. However, voltage sources that can be found in real circuits are never ideal as they present an internal resistance (RS) that dissipates a fraction of the power they produce. This internal resistance is a modelization that reflects some dissipation phenomena, the component is not physically present in the design of the voltage source. Real voltage sources have a V/I ...
Triboelectric nanogenerators (TENG) convert mechanical energy harvested from the environment to electricity for powering small devices such as sensors or for recharging consumer electronics. Now, researchers have harnessed ...
An AC generator, also called an alternator, is a device that converts mechanical energy into electrical energy. AC stands for alternating current. The device generates alternating voltage by...
An alternator is an electrical generator that converts mechanical energy to electrical energy in the form of alternating current.
Using a unique single-molecule force measurement tool, a research team has developed a clearer understanding of how platelets sense the me
Mechanobiology and Extracellular Matrix Remodeling in Disease The health and viability of soft tissues are closely governed by the mechanobiology of cells and their surrounding extracellular matrix (ECM). It is also known that the organization and stiffness of the ECM play an integral role in many human diseases. Research efforts within the STBL are therefore…