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Aranzazu Del Campo, Roshna V Nair, Aleeza Farrukh
The integrin α5β1 is overexpressed in colon, breast, ovarian, lung and brain tumors and has been identified as key component in mechanosensing. In order to study how dynamic changes of α5β1 engagement affect cellular behaviour, photoactivatable derivatives of α5β1 specific ligands are presented in this article. A photoremovable protecting group (PRPG) was introduced into the ligand structure at a relevant position for integrin recognition. The presence of the chromophore temporally inhibited ligand bioactivity...
May 18, 2018: Chembiochem: a European Journal of Chemical Biology
Dag Arne Lihaug Hoff, Barry McMahon, Hans Gregersen
Esophageal mechanosensation describes the relationship between a mechanical stimulation of the esophageal wall, such as bag distension, and the reaction to the stimulation perceived or unperceived. When studying mechanosensation in esophageal disease, it is important to recognize that symptoms might be due to alterations at different levels of the neuromuscular system, such as alterations at the mechanoreceptor level or in the afferent mechanosensory pathways, or irregularities in the homeostatic state. One might ask if it is possible to provoke, record, and describe the multidimensional responses behind a mechanosensory experience? It is a complex system and, at a minimum, a multidisciplinary approach is needed to avoid erroneous conclusions...
May 16, 2018: Annals of the New York Academy of Sciences
Rafael Gonzalez-Cano, Bruno Boivin, Daniel Bullock, Laura Cornelissen, Nick Andrews, Michael Costigan
Most pathological pain conditions in patients and rodent pain models result in marked alterations in mechanosensation and the gold standard way to measure this is by use of von Frey fibers. These graded monofilaments are used to gauge the level of stimulus-evoked sensitivity present in the affected dermal region. One of the most popular methods used to determine von Frey thresholds is the up-down testing paradigm introduced by Dixon for patients in 1980 and by Chapman and colleagues for rodents in 1994. Although the up-down method is very accurate, leading to its widespread use, defining the 50% threshold from primary data is complex and requires a relatively time-consuming analysis step...
2018: Frontiers in Pharmacology
Qi Li, Niraj K Nirala, Yingchao Nie, Hsi-Ju Chen, Gary Ostroff, Junhao Mao, Qi Wang, Lan Xu, Y Tony Ip
The intestinal epithelium has a high cell turnover rate and is an excellent system to study stem cell-mediated adaptive growth. In the Drosophila midgut, the Ste20 kinase Misshapen, which is distally related to Hippo, has a niche function to restrict intestinal stem cell activity. We show here that, under low growth conditions, Misshapen is localized near the cytoplasmic membrane, is phosphorylated at the threonine 194 by the upstream kinase Tao, and is more active toward Warts, which in turn inhibits Yorkie...
May 9, 2018: Developmental Cell
Shujie Shi, Stephanie M Mutchler, Brandon M Blobner, Ossama B Kashlan, Thomas R Kleyman
The Caenorhabditis elegans MEC-4/MEC-10 channel mediates the worm's response to gentle body touch and is activated by laminar shear stress (LSS) when expressed in Xenopus oocytes. Substitutions   at multiples sites within the second transmembrane helix (TM2) of MEC-4 or MEC-10 abolish the gentle touch response in worms, but the roles of these residues in mechanosensing are unclear. The present study therefore examined the role of specific MEC-4 and MEC-10 TM2 residues in the channel's response to LSS. We found that introducing mutations within the TM2 of MEC-4 or MEC-10 not only altered channel activity, but also affected the channel's response to LSS...
May 9, 2018: Journal of Biological Chemistry
Hu Zhang, Xiaomin Yue, Hankui Cheng, Xiaoyan Zhang, Yang Cai, Wenjuan Zou, Guifang Huang, Lufeng Cheng, Fang Ye, Lijun Kang
Mechanotransduction is crucial for touch sensation, hearing, proprioception, and pain sensing. In C. elegans, male ray neurons have been implicated to be involved in the mechanosensation required for mating behavior. However, whether ray neurons directly sense mechanical stimulation is not yet known, and the underlying molecular mechanisms have not been identified. Using in vivo calcium imaging, we recorded the touch-induced calcium responses in male ray neurons. Our data demonstrated that ray neurons are sensitive to mechanical stimulation in a neurotransmitter-independent manner...
May 8, 2018: Scientific Reports
Pavan Vedula, Anna Kashina
The actin cytoskeleton plays key roles in every eukaryotic cell and is essential for cell adhesion, migration, mechanosensing, and contractility in muscle and non-muscle tissues. In higher vertebrates, from birds through to mammals, actin is represented by a family of six conserved genes. Although these genes have evolved independently for more than 100 million years, they encode proteins with ≥94% sequence identity, which are differentially expressed in different tissues, and tightly regulated throughout embryogenesis and adulthood...
May 8, 2018: Journal of Cell Science
Bram Piersma, Olaf Y Wouters, Ruud A Bank
Mechanosensing of fibroblasts plays a key role in the development of fibrosis. So far, no effective treatments are available to treat this devastating disorder. Spectrins regulate cell morphology and are potential mechanosensors in a variety of non-erythroid cells, but little is known about the role of spectrins in fibroblasts. We investigate whether αII- and βII-spectrin are required for the phenotypic properties of adult human dermal (myo)fibroblasts. Knockdown of αII- or βII-spectrin in fibroblasts did not affect cell adhesion, cell size and YAP nuclear/cytosolic localization...
May 3, 2018: Cell and Tissue Research
Florian A Gegenfurtner, Berenice Jahn, Helga Wagner, Christoph Ziegenhain, Wolfgang Enard, Ludwig Geistlinger, Joachim O Rädler, Angelika M Vollmar, Stefan Zahler
Developmental processes such as angiogenesis are associated to a constant remodeling of the actin cytoskeleton in response to different mechanical stimuli. The mechanosensitive transcription factors MRTF and YAP are important mediators of this challenging adaptation process. However, it is yet unknown whether both pathways respond identical or divergent to a given microenvironmental guidance cue. Here, we use a micropatterning approach to dissect single aspects of cellular behavior in a spatiotemporally controllable setting...
May 3, 2018: Journal of Cell Science
Courtney Scerbak, Elena Vayndorf, Alicia Hernandez, Colin McGill, Barbara Taylor
Medicinal berries are appreciated for their health benefits, in traditional ecological knowledge and nutrition science. Determining the cellular mechanisms underlying the effects of berry supplementation may contribute to our understanding of aging. Here, we report that lowbush cranberry (Vaccinium vitis-idaea) treatment causes marked nuclear localization of the central aging-related transcription factor DAF-16/FOXO in aged Caenorhabditis elegans. Further, functional DAF-16 is required for the lifespan extension, improved mechanosensation, and posterior touch receptor neuron morphological changes induced by lowbush cranberry treatments...
May 1, 2018: GeroScience
Shier Nee Saw, Yu Wei Poh, Dawn Chia, Arijit Biswas, Citra Nurfarah Zaini Mattar, Choon Hwai Yap
Significant reductions in blood flow and umbilical diameters were reported in pregnancies affected by intrauterine growth restriction (IUGR) from placental insufficiency. However, it is not known if IUGR umbilical blood vessels experience different hemodynamic wall shear stresses (WSS) compared to normal umbilical vessels. As WSS is known to influence vasoactivity and vascular growth and remodeling, which can regulate flow rates, it is important to study this parameter. In this study, we aim to characterize umbilical vascular WSS environment in normal and IUGR pregnancies, and evaluate correlation between WSS and vascular diameter, and gestational age...
April 24, 2018: Biomechanics and Modeling in Mechanobiology
Valeria Davì, Hirokazu Tanimoto, Dmitry Ershov, Armin Haupt, Henry De Belly, Rémi Le Borgne, Etienne Couturier, Arezki Boudaoud, Nicolas Minc
How growing cells cope with size expansion while ensuring mechanical integrity is not known. In walled cells, such as those of microbes and plants, growth and viability are both supported by a thin and rigid encasing cell wall (CW). We deciphered the dynamic mechanisms controlling wall surface assembly during cell growth, using a sub-resolution microscopy approach to monitor CW thickness in live rod-shaped fission yeast cells. We found that polar cell growth yielded wall thinning and that thickness negatively influenced growth...
April 23, 2018: Developmental Cell
Mridula Balakrishnan, Mary K Baylies
In this issue of Developmental Cell, Tan et al. (2018) show how a novel player in myonuclear positioning, the ubiquitin ligase Ari-1, regulates levels of Koi, a member of the LINC mechanosensing complex, and affects nuclear morphology and positioning in both Drosophila muscles and human vascular smooth muscle cells.
April 23, 2018: Developmental Cell
Heemin Kang, Hee Joon Jung, Dexter Siu Hong Wong, Sung Kyu Kim, Sien Lin, Kai Fung Chan, Li Zhang, Gang Li, Vinayak P Dravid, Liming Bian
Remote, non-invasive, and reversible control over the nanoscale presentation of bioactive ligands, such as Arg-Gly-Asp (RGD) peptide, is highly desirable for temporally regulating cellular functions in vivo. Herein, we present a novel strategy for physically uncaging RGD using a magnetic field that allows safe and deep tissue penetration. We developed a heterodimeric nanoswitch consisting of a magnetic nanocage (MNC) coupled to an underlying RGD-coated gold nanoparticle (AuNP) via a long flexible linker. Magnetically controlled movement of MNC relative to AuNP allowed reversible uncaging and caging of RGD that modulate physical accessibility of RGD for integrin binding, thereby regulating stem cell adhesion, both in vitro and in vivo...
April 22, 2018: Journal of the American Chemical Society
Lara Cristóbal, Miguel A Ortega, Ángel Asúnsolo, Beatriz Romero, Melchor Álvarez-Mon, Julia Buján, Andrés A Maldonado, Natalio García-Honduvilla
Despite advances in regenerative medicine and tissue engineering, human skin substitutes remain a clear goal to achieve. Autografts remain the principal clinical option. The long-term changes in dermis, as well as its response after injuries, are not well known. Research in this field has been hindered by a lack of experimental animal models. This study analyzes the architectural dermal scaffold (collagen and elastin fibers plus fibrillin-microfibrils) changes in a model of human skin pressure ulcers in mice...
April 17, 2018: Histology and Histopathology
Qiuxiang Zhang, Suna Li, Hiu-Tung C Wong, Xinyi J He, Alisha Beirl, Ronald S Petralia, Ya-Xian Wang, Katie S Kindt
Analysis of mechanotransduction among ensembles of sensory hair cells in vivo is challenging in many species. To overcome this challenge, we used optical indicators to investigate mechanotransduction among collections of hair cells in intact zebrafish. Our imaging reveals a previously undiscovered disconnect between hair-cell mechanosensation and synaptic transmission. We show that saturating mechanical stimuli able to open mechanically gated channels are unexpectedly insufficient to evoke vesicle fusion in the majority of hair cells...
April 11, 2018: Nature Communications
Yong Xie, Yanpan Gao, Licheng Zhang, Yanyu Chen, Wei Ge, Peifu Tang
Exosomes are secreted into the blood by various types of cells. These extracellular vesicles are involved in the contribution of exosomal proteins to osteoblastic or osteoclastic regulatory networks during the failure of bone remodeling, which results in age-related bone loss. However, the molecular changes in serum-derived exosomes (SDEs) from aged patients with low bone density and their functions in bone remodeling remain to be fully elucidated. We present a quantitative proteomics analysis of exosomes purified from the serum of the elderly patients with osteoporosis/osteopenia and normal volunteers; these data are available via Proteome Xchange with the identifier PXD006463...
March 30, 2018: Aging Cell
Nicole Scholz
In mammals, numerous organ systems are equipped with adhesion G protein-coupled receptors (aGPCRs) to shape cellular processes including migration, adhesion, polarity and guidance. All of these cell biological aspects are closely associated with tumor cell biology. Consistently, aberrant expression or malfunction of aGPCRs has been associated with dysplasia and tumorigenesis. Mounting evidence indicates that cancer cells comprise viscoelastic properties that are different from that of their non-tumorigenic counterparts, a feature that is believed to contribute to the increased motility and invasiveness of metastatic cancer cells...
2018: Frontiers in Oncology
Jiro Takito, Satoshi Inoue, Masanori Nakamura
Osteoclasts form a specialized cell-matrix adhesion structure, known as the "sealing zone", during bone resorption. The sealing zone is a dynamic actin-rich structure that defines the resorption area of the bone. The detailed dynamics and fine structure of the sealing zone have been elusive. Osteoclasts plated on glass do not form a sealing zone, but generate a separate supra-molecular structure called the "podosome belt". Podosomes are integrin-based adhesion complexes involved in matrix adhesion, cell migration, matrix degradation, and mechanosensing...
March 26, 2018: International Journal of Molecular Sciences
Liping Wang, Jianghui Dong, Cory J Xian
Osteocytes, the major type of bone cells embedded in the bone matrix and surrounded by the lacunar and canalicular system, can serve as biomechanosensors and biomechanotranducers of the bone. Theoretical analytical methods have been employed to investigate the biomechanical responses of osteocytes in vivo; the poroelastic properties have not been taken into consideration in the three-dimensional (3D) finite element model. In this study, a 3D poroelastic idealized finite element model was developed and was used to predict biomechanical behaviours (maximal principal strain, pore pressure, and fluid velocity) of the osteocyte-lacunar-canalicular system under 150-, 1000-, 3000-, and 5000-microstrain compressive loads, respectively, representing disuse, physiological, overuse, and pathological overload loading stimuli...
2018: BioMed Research International
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