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"Directional migration"

Svenja F B Mennens, Matteo Bolomini-Vittori, Jorieke Weiden, Ben Joosten, Alessandra Cambi, Koen van den Dries
Dendritic cells (DCs) are specialized immune cells that scan peripheral tissues for foreign material or aberrant cells and, upon recognition of such danger signals, travel to lymph nodes to activate T cells and evoke an immune response. For this, DCs travel large distances through the body, encountering a variety of microenvironments with different mechanical properties such as tissue stiffness. While immune-related pathological conditions such as fibrosis or cancer are associated with tissue stiffening, the role of tissue stiffness in regulating key functions of DCs has not been studied yet...
December 13, 2017: Scientific Reports
Jacob A M Nuhn, Anai M Perez, Ian C Schneider
Cancer cell metastasis is responsible for approximately 90% of deaths related to cancer. The migration of cancer cells away from the primary tumor and into healthy tissue is driven in part by contact guidance, or directed migration in response to aligned extracellular matrix. While contact guidance has been a focus of many studies, much of this research has explored environments that present 2D contact guidance structures. Contact guidance environments in 3D more closely resemble in vivo conditions and model cell-ECM interactions better than 2D environments...
November 28, 2017: Acta Biomaterialia
Tamaghna Gupta, Ritwick Ghosh, Ranjan Ganguly
Acoustophoresis is rapidly gaining prominence in the field of cell manipulation. In recent years, researchers have extensively used this method for separating different types of cells from the bulk fluid. In this paper, we propose a novel acoustophoresis based technique to capture infected or abnormal erythrocytes from blood plasma. A typical acoustic device consisting of a transducer assembly, microfluidic cavity and a reflector is considered. Based on the concept of impedance matching a pair of antibody-coated polystyrene layers is placed in the nodal regions of an acoustic field within the cavity...
November 27, 2017: International Journal for Numerical Methods in Biomedical Engineering
Abdullah Al Mosabbir, Kevin Truong
Protein-based systems for light directed migration of cells have been demonstrated up to distances of several hundred microns, but larger distances in the centimeter scale would allow new possible applications. Light activated migration in mammalian cells can be achieved by cells expressing channelrhodopsin-2 and an engineered Ca2+ sensitive Rac1 protein called RACer. In this study, light was used to induce wound healing, localize cells into a region of interest, and move cells over centimeter scale distances...
November 26, 2017: Small GTPases
Caren E Petrie Aronin, Yun M Zhao, Justine S Yoon, Nicole Y Morgan, Thorsten Prüstel, Ronald N Germain, Martin Meier-Schellersheim
Chemoattractant-mediated recruitment of hematopoietic cells to sites of pathogen growth or tissue damage is critical to host defense and organ homeostasis. Chemotaxis is typically considered to rely on spatial sensing, with cells following concentration gradients as long as these are present. Utilizing a microfluidic approach, we found that stable gradients of intermediate chemokines (CCL19 and CXCL12) failed to promote persistent directional migration of dendritic cells or neutrophils. Instead, rising chemokine concentrations were needed, implying that temporal sensing mechanisms controlled prolonged responses to these ligands...
November 21, 2017: Immunity
Srikanth Budnar, Alpha S Yap
α-catenin is a scaffolding molecule that can bind F-actin and other cytoskeletal proteins. It is best known for its contribution to cell-cell adhesion. In this issue of Developmental Cell, Vassilev et al. (2017) identify an extrajunctional pool of α-catenin that regulates RhoA signaling and controls directional migration of single cells.
November 20, 2017: Developmental Cell
Yulia Artemenko, Peter N Devreotes
Chemotaxis, or migration up a gradient of a chemoattractant, is the best understood mode of directed migration. Studies using social amoeba Dictyostelium discoideum revealed that a complex signal transduction network of parallel pathways amplifies the response to chemoattractants, and leads to biased actin polymerization and protrusion of a pseudopod in the direction of a gradient. In contrast, molecular mechanisms driving other types of directed migration, for example, due to exposure to shear flow or electric fields, are not known...
November 9, 2017: Journal of Visualized Experiments: JoVE
Shaobo Wang, Bianka Brunne, Shanting Zhao, Xuejun Chai, Jiawei Li, Jeremie Lau, Antonio Virgilio Failla, Bernd Zobiak, Mirjam Sibbe, Gary L Westbrook, David Lutz, Michael Frotscher
Reelin controls neuronal migration and layer formation. Previous studies in reeler mice deficient in Reelin focused on the result of the developmental process in fixed tissue sections. It has remained unclear whether Reelin affects the migratory process, migration directionality or migrating neurons guided by the radial glial scaffold. Moreover, Reelin has been regarded as an attractive signal, since newly generated neurons migrate toward the Reelin-containing marginal zone. Conversely, Reelin might be a stop signal, since migrating neurons in reeler, but not in wild-type mice, invade the marginal zone...
November 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Megan L Norris, Andrea Pauli, James A Gagnon, Nathan D Lord, Katherine W Rogers, Christian Mosimann, Leonard I Zon, Alexander F Schier
Toddler/Apela/Elabela is a conserved secreted peptide that regulates mesendoderm development during zebrafish gastrulation. Two non-exclusive models have been proposed to explain Toddler function. The 'specification model' postulates that Toddler signaling enhances Nodal signaling to properly specify endoderm, whereas the 'migration model' posits that Toddler signaling regulates mesendodermal cell migration downstream of Nodal signaling. Here, we test key predictions of both models. We find that in toddler mutants Nodal signaling is initially normal and increasing endoderm specification does not rescue mesendodermal cell migration...
November 9, 2017: ELife
Nikita A Mitkin, Alisa M Muratova, George V Sharonov, Kirill V Korneev, Ekaterina N Sviriaeva, Dmitriy Mazurov, Anton M Schwartz, Dmitry V Kuprash
Many types of chemotherapeutic agents induce of DNA-damage that is accompanied by activation of p53 tumor suppressor, a key regulator of tumor development and progression. In our previous study we demonstrated that p53 could repress CXCR5 chemokine receptor gene in MCF-7 breast cancer cells via attenuation of NFkB activity. In this work we aimed to determine individual roles of p53 family members in the regulation of CXCR5 gene expression under genotoxic stress. DNA-alkylating agent methyl methanesulfonate caused a reduction in CXCR5 expression not only in parental MCF-7 cells but also in MCF-7-p53off cells with CRISPR/Cas9-mediated inactivation of the p53 gene...
November 6, 2017: Biochimica et Biophysica Acta
Vassil Vassilev, Anna Platek, Sylvain Hiver, Hideki Enomoto, Masatoshi Takeichi
Cell migration plays a pivotal role in morphogenetic and pathogenetic processes. To achieve directional migration, cells must establish a front-to-rear axis of polarity. Here we show that components of the cadherin-catenin complex function to stabilize this front-rear polarity. Neural crest and glioblastoma cells undergo directional migration in vivo or in vitro. During this process, αE-catenin accumulated at lamellipodial membranes and then moved toward the rear with the support of a tyrosine-phosphorylated β-catenin...
November 20, 2017: Developmental Cell
Lorenz Fülle, Nancy Steiner, Markus Funke, Fabian Gondorf, Franziska Pfeiffer, Julia Siegl, Friederike V Opitz, Silvana K Haßel, Anna Belen Erazo, Oliver Schanz, H James Stunden, Michael Blank, Carsten Gröber, Kristian Händler, Marc Beyer, Heike Weighardt, Eicke Latz, Joachim L Schultze, Günter Mayer, Irmgard Förster
The chemokine CCL17, mainly produced by dendritic cells (DCs) in the immune system, is involved in the pathogenesis of various inflammatory diseases. As a ligand of CCR4, CCL17 induces chemotaxis and facilitates T cell-DC interactions. We report the identification of two novel RNA aptamers, which were validated in vitro and in vivo for their capability to neutralize CCL17. Both aptamers efficiently inhibited the directed migration of the CCR4(+) lymphoma line BW5147.3 toward CCL17 in a dose-dependent manner...
October 13, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
L S Litvinova, V V Shupletsova, K A Yurova, O G Khaziakhmatova, N M Todosenko, M Yu Khlusova, G B Slepchenko, E G Cherempey, Yu P Sharkeev, E G Komarova, M B Sedelnikova, V V Malashchenko, E S Melashchenko, I A Khlusov
The Cell-IQ continuous surveillance system allowed us to establish the following changes in a 14- day culture in vitro: a twofold suppression of the directional migration of multipotent mesenchymal stromal cells of human adipose tissue (MMSC-AT) towards the samples with a microarc calcium phosphate (CP) coating from synthetic hydroxyapatite; a tenfold decrease in the cell mass on the interphase with the samples, which was accompanied by a slight reduction in the expression of membrane determinants of stromal stem cells; and an enhancement of their osteogenic differentiation (osteocalcin secretion and mineralized matrix formation) on the 21st day of the study...
September 2017: Doklady. Biochemistry and Biophysics
Li-Li Ma, Lan Shen, Gui-Hui Tong, Na Tang, Yang Luo, Li-Li Guo, Chun-Ting Hu, Ying-Xin Huang, Guan Huang, Fang-Yan Jing, Chao Liu, Zhuo-Yi Li, Na Zhou, Qian-Wen Yan, Yan Lei, Shi-Jie Zhu, Zhi-Qiang Cheng, Guang-Wen Cao, Yong-Jian Deng, Yan-Qing Ding
Directional migration is a cost-effective movement allowing invasion and metastatic spread of cancer cells. Although migration related to cytoskeletal assembly and microenvironmental chemotaxis has been elucidated, little is known about interaction between extracellular and intracellular molecules for controlling the migrational directionality. A polarized expression of prohibitin (PHB) in the front ends of CRC cells favors metastasis and is correlated with poor prognosis for 545 CRC patients. A high level of vascular endothelial growth factor (VEGF) in the interstitial tissue of CRC patients is associated with metastasis...
September 29, 2017: Oncotarget
Marine Bretou, Pablo J Sáez, Doriane Sanséau, Mathieu Maurin, Danielle Lankar, Melanie Chabaud, Carmine Spampanato, Odile Malbec, Lucie Barbier, Shmuel Muallem, Paolo Maiuri, Andrea Ballabio, Julie Helft, Matthieu Piel, Pablo Vargas, Ana-Maria Lennon-Duménil
Dendritic cells (DCs) patrol their environment by linking antigen acquisition by macropinocytosis to cell locomotion. DC activation upon bacterial sensing inhibits macropinocytosis and increases DC migration, thus promoting the arrival of DCs to lymph nodes for antigen presentation to T cells. The signaling events that trigger such changes are not fully understood. We show that lysosome signaling plays a critical role in this process. Upon bacterial sensing, lysosomal calcium is released by the ionic channel TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1), which activates the actin-based motor protein myosin II at the cell rear, promoting fast and directional migration...
October 27, 2017: Science Immunology
Takamasa Mizoguchi, Shoko Ikeda, Saori Watanabe, Michiko Sugawara, Motoyuki Itoh
Persistent directional cell migration is involved in animal development and diseases. The small GTPase Rac1 is involved in F-actin and focal adhesion dynamics. Local Rac1 activity is required for persistent directional migration, whereas global, hyperactivated Rac1 enhances random cell migration. Therefore, precise control of Rac1 activity is important for proper directional cell migration. However, the molecular mechanism underlying the regulation of Rac1 activity in persistent directional cell migration is not fully understood...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
Svetlana A Fayngerts, Zhaojun Wang, Ali Zamani, Honghong Sun, Amanda E Boggs, Thomas P Porturas, Weidong Xie, Mei Lin, Terry Cathopoulis, Jason R Goldsmith, Anastassios Vourekas, Youhai H Chen
The polarization of leukocytes toward chemoattractants is essential for the directed migration (chemotaxis) of leukocytes. How leukocytes acquire polarity after encountering chemical gradients is not well understood. We found here that leukocyte polarity was generated by TIPE2 (TNFAIP8L2), a transfer protein for phosphoinositide second messengers. TIPE2 functioned as a local enhancer of phosphoinositide-dependent signaling and cytoskeleton remodeling, which promoted leading-edge formation. Conversely, TIPE2 acted as an inhibitor of the GTPase Rac, which promoted trailing-edge polarization...
December 2017: Nature Immunology
Riina Kaukonen, Guillaume Jacquemet, Hellyeh Hamidi, Johanna Ivaska
2D surfaces offer simple analysis of cells in culture, yet these often yield different cell morphologies and responses from those observed in vivo. Considerable effort has therefore been expended on the generation of more tissue-like environments for the study of cell behavior in vitro. Purified matrix proteins provide a 3D scaffold that better mimics the in vivo situation; however, these are far removed from the complex tissue composition seen in vivo. Cell-derived matrices (CDMs) offer a more physiologically relevant alternative for studying in vivo-like cell behavior in vitro...
November 2017: Nature Protocols
Fatemeh Dubois, Kyle Alpha, Christopher E Turner
Cell polarization and directed migration play pivotal roles in diverse physiological and pathological processes. Herein, we identify new roles for paxillin-mediated HDAC6 inhibition in regulating key aspects of cell polarization in both 2D and 1D matrix environments. Paxillin, by modulating microtubule acetylation through HDAC6 regulation, was shown to control centrosome and Golgi reorientation towards the leading edge, a hallmark of cell polarization to ensure directed trafficking of promigratory factors. Paxillin was also required for pericentrosomal Golgi localization and centrosome cohesion, independent of its localization to, and role in, focal adhesion signaling...
October 18, 2017: Molecular Biology of the Cell
Koceila Aizel, Andrew G Clark, Anthony Simon, Sara Geraldo, Anette Funfak, Pablo Vargas, Jérôme Bibette, Danijela Matic Vignjevic, Nicolas Bremond
In many cell types, migration can be oriented towards a chemical stimulus. In mammals, for example, embryonic cells migrate to follow developmental cues, immune cells migrate toward sites of inflammation, and cancer cells migrate away from the primary tumour and toward blood vessels during metastasis. Understanding how cells migrate in 3D environments in response to chemical cues is thus crucial to understanding directed migration in normal and disease states. To date, chemotaxis in mammalian cells has been primarily studied using 2D migration models...
November 7, 2017: Lab on a Chip
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