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Mateusz M Urbanski, Carmen V Melendez-Vasquez
Extracellular matrix (ECM) elasticity may direct cellular differentiation and can be modeled in vitro using synthetic ECM-like substrates with defined elastic properties. However, the effectiveness of such approaches depends on the selection of a range of elasticity and ECM ligands that accurately model the relevant tissue. Here, we present a cell culture system than can be used to study Schwann cell differentiation on substrates which model the changes in mechanical ECM properties that occur during sciatic nerve development...
2018: Methods in Molecular Biology
Congyu Wu, Yajing Shen, Mengwei Chen, Kun Wang, Yongyong Li, Yu Cheng
Remote control of cells and the regulation of cell events at the molecular level are of great interest in the biomedical field. In addition to chemical compounds and genes, mechanical forces play a pivotal role in regulating cell fate, which have prompted the rapid growth of mechanobiology. From a perspective of nanotechnology, magnetic nanomaterials (MNs) are an appealing option for mechanotransduction due to their capabilities in spatiotemporal manipulation of mechanical forces via the magnetic field. As a newly developed paradigm, magneto-mechanotransduction is harnessed to physically regulate cell fate for biomedical applications...
March 15, 2018: Advanced Materials
Jungmok Seo, Jung-Youn Shin, Jeroen Leijten, Oju Jeon, Ayça Bal Öztürk, Jeroen Rouwkema, Yuancheng Li, Su Ryon Shin, Hadi Hajiali, Eben Alsberg, Ali Khademhosseini
Biophysical cues can potently direct a cell's or tissue's behavior. Cells interpret their biophysical surroundings, such as matrix stiffness or dynamic mechanical stimulation, through mechanotransduction. However, our understanding of the various aspects of mechanotransduction has been limited by the lack of proper analysis platforms capable of screening three-dimensional (3D) cellular behaviors in response to biophysical cues. Here, we developed a dynamic compression bioreactor to study the combinational effects of biomaterial composition and dynamic mechanical compression on cellular behavior in 3D hydrogels...
March 15, 2018: ACS Applied Materials & Interfaces
Yoshinori Hirano, Yu Amano, Shigenobu Yonemura, Toshio Hakoshima
Mechanotransduction by α-catenin facilitates the force-dependent development of adherens junctions (AJs) by recruiting vinculin to reinforce actin anchoring of AJs. The α-catenin mechanotransducing action is facilitated by its force-sensing device region that autoinhibits the vinculin-binding site 1 (VBS1). Here, we report the high-resolution structure of the force-sensing device region of α-catenin, which shows the autoinhibited form comprised of helix bundles E, F and G. The cryptic VBS1 is embedded into helix bundle E stabilized by direct interactions with the autoinhibitory region forming helix bundles F and G...
March 15, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Yan Li, Dewen Ye, Mingxi Li, Ming Ma, Ning Gu
The paper provides a brief overview of the use of iron oxide nanoparticles (IONPs) in the areas of bone regenerative medicine. Reconstruction of bone defects caused by trauma, non-union, and bone tumour excision still faces many challenges despite the intense investigations and advancement in bone tissue engineering and bone regeneration over the past decades. IONPs have promising prospects in this field due to their controlled responsive characteristics in specific external magnetic fields and have been of great interest during the last few years...
March 14, 2018: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
Ben Warren, Tom Matheson
Insect auditory receivers provide an excellent comparative resource to understand general principles of auditory transduction, but analysis of the electrophysiological properties of the auditory neurons has been hampered by their tiny size and inaccessibility. Here we pioneer patch-clamp recordings from the auditory neurons of Müller-s Organ of the desert locust Schistocerca gregaria to characterise dendritic spikes, axonal spikes and the transduction current. We demonstrate that dendritic spikes, elicited by sound stimuli, trigger axonal spikes, and that both types are sodium- and voltage-dependent and blocked by TTX...
March 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Joyjyoti Das, Somnath Maji, Tarun Agarwal, Suman Chakraborty, Tapas K Maiti
During metastatic dissemination, cancer cells experience shear stresses in narrow confinements of in vivo vasculature. Such stresses are currently known to influence a gamut of cellular processes. While a host of cells emanating from a primary tumor perish in circulation due to shear, some cells manage to migrate to distant niches and form secondary tumors. Current research focuses on how cancer cells avert such mechanical stresses and adapt themselves in order to survive. This study deals with the autophagic response of cervical cancer cells HeLa and its subline HeLa 229, exposed to physiological shear stresses in vitro, and evaluates its role as a pro-survival mechanism...
March 13, 2018: Clinical & Experimental Metastasis
Min Jiang, Qiang Lyu, Yun-Gang Bai, Huan Liu, Jing Yang, Jiu-Hua Cheng, Ming Zheng, Jin Ma
Recent studies have suggested that microgravity-induced arterial remodelling contributes to post-flight orthostatic intolerance and that multiple mechanisms are involved in arterial remodelling. However, the initial mechanism by which haemodynamic changes induce arterial remodelling is unknown. Focal adhesions (FAs) are dynamic protein complexes that have mechanotransduction properties. This study aimed to investigate the role of FAs in simulated microgravity-induced basilar and femoral arterial remodelling...
March 11, 2018: Canadian Journal of Physiology and Pharmacology
VijayKrishna Raghunathan, Julia Benoit, Ramesh Kasetti, Gulab Zode, Michelle Salemi, Brett S Phinney, Kate E Keller, Julia A Staverosky, Christopher J Murphy, Ted Acott, Janice Vranka
Ocular hypertension is a causal risk-factor to developing glaucoma. This is associated with stiffening of the trabecular meshwork (TM), the primary site of resistance to aqueous-humor-outflow. The mechanisms underlying this stiffening or how pathologic extracellular matrix (ECM) affects cell function are poorly understood. It is recognized that mechanotransduction systems allow cells to sense and translate the intrinsic biophysical properties of ECM into intracellular signals to control gene transcription, protein expression, and cell behavior...
March 7, 2018: Acta Biomaterialia
Benjamin Yeung, Prem Khanal, Virja Mehta, Laura Trinkle-Mulcahy, Xiaolong Yang
The Hippo pathway is a signalling cascade that plays important roles in organ size control, tumorigenesis, metastasis, stress response, stem cell differentiation and renewal during development and tissue homeostasis, and mechanotransduction. Recently, we and others have shown that loss of the Hippo pathway core component LATS or overexpression of its downstream targets YAP and its paralog TAZ causes resistance of cancer cells to anti-tubulin drugs. However, YAP and TAZ mediates anti-tubulin drug-induced apoptosis independent of its upstream regulator LATS and the Hippo pathway...
March 9, 2018: Molecular Cancer Research: MCR
Pratibha Narayanan, Meike Hütte, Galina Kudryasheva, Francisco J Taberner, Stefan G Lechner, Florian Rehfeldt, David Gomez-Varela, Manuela Schmidt
Piezo2 ion channels are critical determinants of the sense of light touch in vertebrates. Yet, their regulation is only incompletely understood. We recently identified myotubularin related protein-2 (Mtmr2), a phosphoinositide (PI) phosphatase, in the native Piezo2 interactome of murine dorsal root ganglia (DRG). Here, we demonstrate that Mtmr2 attenuates Piezo2-mediated rapidly adapting mechanically activated (RA-MA) currents. Interestingly, heterologous Piezo1 and other known MA current subtypes in DRG appeared largely unaffected by Mtmr2...
March 9, 2018: ELife
Eek-Hoon Jho
Since the first component of Hippo signaling, Wts in Drosophila, was identified in 1995, the progress of Hippo signaling studies has been very slow initially. However, after the findings suggesting that the core kinase pathway established in Drosophila was evolutionarily conserved in metazoans for the determination of organ size around 2008, the number of publications related to Hippo signaling has grown exponentially. Identification of molecular mechanisms underlying Hippo signaling response to intrinsic cues, such as cell-cell contact and mechanotransduction, as well as extrinsic cues, such as nutrients and soluble factors, has been one of the key topics of Hippo signaling...
March 9, 2018: BMB Reports
Clive P Morgan, Hongyu Zhao, Meredith LeMasurier, Wei Xiong, Bifeng Pan, Piotr Kazmierczak, Matthew R Avenarius, Michael Bateschell, Ruby Larisch, Anthony J Ricci, Ulrich Müller, Peter G Barr-Gillespie
Hair cells of the inner ear transduce mechanical stimuli like sound or head movements into electrical signals, which are propagated to the central nervous system. The hair-cell mechanotransduction channel remains unidentified. We tested whether three transient receptor channel (TRP) family members, TRPV6, TRPM6 and TRPM7, were necessary for transduction. TRPV6 interacted with USH1C (harmonin), a scaffolding protein that participates in transduction. Using a cysteine-substitution knock-in mouse line and methanethiosulfonate (MTS) reagents selective for this allele, we found that inhibition of TRPV6 had no effect on transduction in mouse cochlear hair cells...
2018: Frontiers in Cellular Neuroscience
Jared Hennen, Cosmo A Saunders, Joachim D Mueller, G W Gant Luxton
Linker of nucleoskeleton and cytoskeleton (LINC) complexes are conserved molecular bridges within the nuclear envelope that mediate mechanical force transmission into the nucleoplasm. The core of the LINC complex is formed by a transluminal interaction between the outer and inner nuclear membrane KASH and SUN proteins, respectively. Mammals encode six KASH proteins and five SUN proteins. Recently, KASH proteins were shown to bind to the domain interfaces of trimeric SUN2 proteins in vitro However neither the existence of SUN2 trimers in living cells nor the extent to which other SUN proteins conform to this assembly state have been tested experimentally...
March 7, 2018: Molecular Biology of the Cell
Patrick Lacolley, Veronique Regnault, Alberto P Avolio
Arterial aging engages a plethora of key signalling pathways that act in concert to induce vascular smooth muscle cell (VSMC) phenotypic changes leading to vascular degeneration and extracellular matrix degradation responsible for alterations of the mechanical properties of the vascular wall. This review highlights proof-of-concept examples of components of the extracellular matrix, VSMC receptors which connect extracellular and intracellular structures, and signalling pathways regulating changes in mechanotransduction and vascular homeostasis in aging...
March 15, 2018: Cardiovascular Research
Nuno M Coelho, Christopher A McCulloch
The preservation of tissue and organ architecture and function depends on tightly regulated interactions of cells with the extracellular matrix (ECM). These interactions are maintained in a dynamic equilibrium that balances intracellular, myosin-generated tension with extracellular resistance conferred by the mechanical properties of the extracellular matrix. Disturbances of this equilibrium can lead to the development of fibrotic lesions that are associated with a wide repertoire of high prevalence diseases including obstructive cardiovascular diseases, muscular dystrophy and cancer...
March 7, 2018: Cell Adhesion & Migration
Ahmed El Kaffas, Azza Al-Mahrouki, Amr Hashim, Niki Law, Anoja Giles, Gregory J Czarnota
Background: High-dose radiotherapy (>8-10 Gy) causes rapid endothelial cell death via acid sphingomyelinase (ASMase)-induced ceramide production, resulting in biologically significant enhancement of tumor responses. To further augment or solicit similar effects at low radiation doses, we used genetic and chemical approaches to evaluate mechano-acoustic activation of the ASMase-ceramide pathway by ultrasound-stimulated microbubbles (USMB). Methods: Experiments were carried out in wild-type and acid sphingomyelinase (asmase) knockout mice implanted with fibrosarcoma xenografts...
February 28, 2018: Journal of the National Cancer Institute
Estee L George, Sharon L Truesdell, Spencer L York, Marnie M Saunders
Researchers have been using lab-on-a-chip systems to isolate factors for study, simulate laboratory analysis and model cellular, tissue and organ level processes. The technology is increasing rapidly, but the bone field has been slow to keep pace. Novel models are needed that have the power and flexibility to investigate the elegant and synchronous multicellular interactions that occur in normal bone turnover and in disease states in which remodeling is implicated. By removing temporal and spatial limitations and enabling quantification of functional outcomes, the platforms should provide unique environments that are more biomimetic than single cell type systems while minimizing complex systemic effects of in vivo models...
February 27, 2018: Experimental Cell Research
Alberto Elosegui-Artola, Xavier Trepat, Pere Roca-Cusachs
The linkage of cells to their microenvironment is mediated by a series of bonds that dynamically engage and disengage, in what has been conceptualized as the molecular clutch model. Whereas this model has long been employed to describe actin cytoskeleton and cell migration dynamics, it has recently been proposed to also explain mechanotransduction (i.e., the process by which cells convert mechanical signals from their environment into biochemical signals). Here we review the current understanding on how cell dynamics and mechanotransduction are driven by molecular clutch dynamics and its master regulator, the force loading rate...
February 26, 2018: Trends in Cell Biology
Michele A Corrigan, Gillian P Johnson, Elena Stavenschi, Mathieu Riffault, Marie-Noelle Labour, David A Hoey
Skeletal homeostasis requires the continued replenishment of the bone forming osteoblast from a mesenchymal stem cell (MSC) population, a process that has been shown to be mechanically regulated. However, the mechanisms by which a biophysical stimulus can induce a change in biochemical signaling, mechanotransduction, is poorly understood. As a precursor to loading-induced bone formation, deciphering the molecular mechanisms of MSC osteogenesis is a critical step in developing novel anabolic therapies. Therefore, in this study we characterize the expression of the mechanosensitive calcium channel Transient Receptor Potential subfamily V member 4 (TRPV4) in MSCs and demonstrate that TRPV4 localizes to areas of high strain, specifically the primary cilium...
February 28, 2018: Scientific Reports
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