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Nascent adhesion

William D Constance, Amrita Mukherjee, Yvette E Fisher, Sinziana Pop, Eric Blanc, Yusuke Toyama, Darren W Williams
Building arborisations of the right size and shape is fundamental for neural network function. Live imaging in vertebrate brains strongly suggests that nascent synapses are critical for branch growth during development. The molecular mechanisms underlying this are largely unknown. Here we present a novel system in Drosophila for studying the development of complex arborisations live, in vivo during metamorphosis. In growing arborisations we see branch dynamics and localisations of presynaptic proteins very similar to the 'synaptotropic growth' described in fish/frogs...
March 5, 2018: ELife
Patrick W Oakes, Tamara C Bidone, Yvonne Beckham, Austin V Skeeters, Guillermina R Ramirez-San Juan, Stephen P Winter, Gregory A Voth, Margaret L Gardel
The ability of adherent cells to sense changes in the mechanical properties of their extracellular environments is critical to numerous aspects of their physiology. It has been well documented that cell attachment and spreading are sensitive to substrate stiffness. Here, we demonstrate that this behavior is actually biphasic, with a transition that occurs around a Young's modulus of ∼7 kPa. Furthermore, we demonstrate that, contrary to established assumptions, this property is independent of myosin II activity...
February 27, 2018: Proceedings of the National Academy of Sciences of the United States of America
S Cavelier, A K Dastjerdi, M D McKee, F Barthelat
The most prominent structural components in bone are collagen and mineral. However, bone additionally contains a substantial amount of noncollagenous proteins (most notably of the SIBLING protein family), some of which may act as cohesive/adhesive "binders" for the composite hybrid collagen/mineral scaffolding, whether in the bulk phase of bone, or at its interfaces. One such noncollagenous protein - osteopontin (OPN) - appears to be critical to the deformability and fracture toughness of bone. In the present study, we used a reconstructed synthetic mineral-OPN-mineral interface, and a biogenic (natural tooth dentin) mineral/collagen-OPN-mineral/collagen interface, to measure the fracture toughness of OPN on mineralized substrates...
February 24, 2018: Bone
Qin Wang, Julie Delcorde, Tracy Tang, Gregory P Downey, Christopher A McCulloch
IL-1 signaling is adhesion-restricted in many cell types, but the mechanism that drives it is not defined. We screened for proteins recruited to nascent adhesions in IL-1-treated human fibroblasts with tandem mass tag-mass spectrometry. We used fibronectin bead preparations to enrich 10 actin-associated proteins. There was a 1.2 times log 2-fold enrichment of actin capping protein (ACP) at 30 min after IL-1 stimulation. Knockdown (KD) of ACP by siRNA reduced IL-1-induced ERK activation(by 56%, matrix metalloproteinase-3 (MMP-3) expression by 48%, and MMP-9 expression by 62% (in all reductions, P < 0...
January 22, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Sannia Sarrach, Yuanchi Huang, Sebastian Niedermeyer, Matthias Hachmeister, Laura Fischer, Sebastian Gille, Min Pan, Brigitte Mack, Gisela Kranz, Darko Libl, Juliane Merl-Pham, Stefanie M Hauck, Elisa Paoluzzi Tomada, Matthias Kieslinger, Irmela Jeremias, Antonio Scialdone, Olivier Gires
Epithelial cell adhesion molecule EpCAM is expressed in pluripotent embryonic stem cells (ESC) in vitro, but is repressed in differentiated cells, except epithelia and carcinomas. Molecular functions of EpCAM, possibly imposing such repression, were primarily studied in malignant cells and might not apply to non-pathologic differentiation. Here, we comprehensively describe timing and rationale for EpCAM regulation in early murine gastrulation and ESC differentiation using single cell RNA-sequencing datasets, in vivo and in vitro models including CRISPR-Cas9-engineered ESC-mutants...
January 29, 2018: Scientific Reports
Junji Itou, Hiroshi Tsukihara, Mamoru Nukatsuka, Masakazu Toi, Teiji Takechi
A drug for metastasis prevention is necessary. The orally administered anticancer drug S-1 contributes to cancer therapy. In a mouse xenograft model of metastatic breast cancer from our previous study, the administration of S-1 inhibited lung metastasis. However, the mechanism of inhibition remains elusive. S-1 contains 5-chloro-2,4-dihydroxypyridine (CDHP), which does not have the antigrowth activity, but prevents the degradation of 5-fluorouracil, an anticancer reagent. In this study, we found that CDHP treatment shrinks cell morphology in metastatic basal-like breast cancer cell lines...
January 22, 2018: Cancer Medicine
Liyun Wang, Robert Keatch, Qi Zhao, John A Wright, Clare E Bryant, Anna L Redmann, Eugene M Terentjev
Biofilm formation on abiotic surfaces in food and medical industry can cause severe contamination and infection, yet how biological and physical factors determine cellular architecture of early biofilms and bacterial behavior of the constituent cells remains largely unknown. In this study we examine the specific role of type-I fimbriae in nascent stages of biofilm formation and the response of micro-colonies to environmental flow shear at single-cell resolution. The results show that type-I fimbriae are not required for reversible adhesion from plankton, but critical for irreversible adhesion of Escherichia coli (E...
January 12, 2018: Applied and Environmental Microbiology
Solomon L Woldu, Ryan C Hutchinson, Laura-Maria Krabbe, Oner Sanli, Vitaly Margulis
Urothelial carcinoma remains a clinical challenge: non-muscle-invasive disease has a high rate of recurrence and risk of progression, and outcomes for patients with advanced disease are poor, owing to a lack of effective systemic therapies. The Rho GTPase family of enzymes was first identified >30 years ago and contains >20 members, which are divided into eight subfamilies: Cdc42, Rac, Rho, RhoUV, RhoBTB, RhoDF, RhoH, and Rnd. Rho GTPases are molecular on-off switches, which are increasingly being understood to have a critical role in a number of cellular processes, including cell migration, cell polarity, cell adhesion, cell cycle progression, and regulation of the cytoskeleton...
February 2018: Nature Reviews. Urology
Yan-Ning Rui, Zhen Xu, Xiaoqian Fang, Miriam R Menezes, Julien Balzeau, Airu Niu, John P Hagan, Dong H Kim
BACKGROUND/AIMS: We recently discovered that harmful variants in THSD1 (Thrombospondin type-1 domain-containing protein 1) likely cause intracranial aneurysm and subarachnoid hemorrhage in a subset of both familial and sporadic patients with supporting evidence from two vertebrate models. The current study seeks to elucidate how THSD1 and patient-identified variants function molecularly in focal adhesions. METHODS: Co-immunostaining and co-immunoprecipitation were performed to define THSD1 subcellular localization and interacting partners...
October 25, 2017: Cellular Physiology and Biochemistry
Kangmin He, Tsuyoshi Sakai, Yoshikazu Tsukasaki, Tomonobu M Watanabe, Mitsuo Ikebe
Filopodia protrude from the leading edge of cells and play important roles in cell motility. Here we report the mechanism of myosin X (encoded by Myo10)-induced multi-cycle filopodia extension. We found that actin, Arp2/3, vinculin and integrin-β first accumulated at the cell's leading edge. Myosin X was then gathered at these sites, gradually clustered by lateral movement, and subsequently initiated filopodia formation. During filopodia extension, we found the translocation of Arp2/3 and integrin-β along filopodia...
October 20, 2017: Scientific Reports
Alexandros Nicolaou, Bernd H Northoff, Kristina Sass, Jana Ernst, Alexander Kohlmaier, Knut Krohn, Christian Wolfrum, Daniel Teupser, Lesca M Holdt
BACKGROUND AND AIMS: In a previous work, a female-specific atherosclerosis risk locus on chromosome (Chr) 3 was identified in an intercross of atherosclerosis-resistant FVB and atherosclerosis-susceptible C57BL/6 (B6) mice on the LDL-receptor deficient (Ldlr(-/-)) background. It was the aim of the current study to identify causative genes at this locus. METHODS: We established a congenic mouse model, where FVB.Chr3(B6/B6) mice carried an 80 Mb interval of distal Chr3 on an otherwise FVB...
September 4, 2017: Atherosclerosis
Ralph T Böttcher, Maik Veelders, Pascaline Rombaut, Jan Faix, Marina Theodosiou, Theresa E Stradal, Klemens Rottner, Roy Zent, Franz Herzog, Reinhard Fässler
Cell spreading requires the coupling of actin-driven membrane protrusion and integrin-mediated adhesion to the extracellular matrix. The integrin-activating adaptor protein kindlin-2 plays a central role for cell adhesion and membrane protrusion by directly binding and recruiting paxillin to nascent adhesions. Here, we report that kindlin-2 has a dual role during initial cell spreading: it binds paxillin via the pleckstrin homology and F0 domains to activate Rac1, and it directly associates with the Arp2/3 complex to induce Rac1-mediated membrane protrusions...
November 6, 2017: Journal of Cell Biology
Seoyoung Son, George J Moroney, Peter J Butler
Integrin-mediated adhesion is a central feature of cellular adhesion, locomotion, and endothelial cell mechanobiology. Although integrins are known to be transmembrane proteins, little is known about the role of membrane biophysics and dynamics in integrin adhesion. We treated human aortic endothelial cells with exogenous amphiphiles, shown previously in model membranes, and computationally, to affect bilayer thickness and lipid phase separation, and subsequently measured single-integrin-molecule adhesion kinetics using an optical trap, and diffusion using fluorescence correlation spectroscopy...
September 5, 2017: Biophysical Journal
Dong Tian, Jinguang Hu, Jie Bao, Richard P Chandra, Jack N Saddler, Canhui Lu
BACKGROUND: Although conversion of low value but high-volume lignin by-product to its usable form is one of the determinant factors for building an economically feasible integrated lignocellulose biorefinery, it has been challenged by its structural complexity and inhomogeneity. We and others have shown that uniform lignin nanoparticles can be produced from a wide range of technical lignins, despite the varied lignocellulosic biomass and the pretreatment methods/conditions applied. This value-added nanostructure lignin enriched with multifunctional groups can be a promising versatile material platform for various downstream utilizations especially in the emerging nanocomposite fields...
2017: Biotechnology for Biofuels
Jose L Gomez-Ballesteros, Perla B Balbuena
Achieving a better control of the nucleation and growth of single-walled carbon nanotubes requires understanding of the changes in the catalyst structure and the interfacial phenomena occurring at the solid surface and the gaseous phase from the early stages of the synthesis process. Carbon nanotubes produced by chemical vapor deposition typically use carbon-philic metal catalysts such as Fe, Ni, and Co, in which both surface C and dissolved C atoms contribute to the nanotube formation. We use density functional theory to investigate the interactions of Rh, a noble metal, with carbon both as individual atoms gradually deposited on the catalyst surface from the precursor gas decomposition and as a nucleating seed adhered to the catalyst...
July 28, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
Javier Moncayo-Arlandi, Ramon Brugada
The intercalated discs that connect cardiomyocytes control cell-to-cell adhesion and communication. Several macromolecular structures (desmosomes, fascia adherens junctions, gap junctions, and sodium-channel complexes) coexist in, and confer their mechanical and electrical properties to, the intercalated disc. Traditionally, each structure was assumed to have a unique function in the intercalated disc. However, growing evidence suggests that these complexes act together in intercellular communication and adhesion, forming a single structural and functional entity - the connexome...
December 2017: Nature Reviews. Cardiology
Bruno Pontes, Pascale Monzo, Laurent Gole, Anabel-Lise Le Roux, Anita Joanna Kosmalska, Zhi Yang Tam, Weiwei Luo, Sophie Kan, Virgile Viasnoff, Pere Roca-Cusachs, Lisa Tucker-Kellogg, Nils C Gauthier
Cell migration is dependent on adhesion dynamics and actin cytoskeleton remodeling at the leading edge. These events may be physically constrained by the plasma membrane. Here, we show that the mechanical signal produced by an increase in plasma membrane tension triggers the positioning of new rows of adhesions at the leading edge. During protrusion, as membrane tension increases, velocity slows, and the lamellipodium buckles upward in a myosin II-independent manner. The buckling occurs between the front of the lamellipodium, where nascent adhesions are positioned in rows, and the base of the lamellipodium, where a vinculin-dependent clutch couples actin to previously positioned adhesions...
September 4, 2017: Journal of Cell Biology
Mehmet Berat Taskin, Dan Xia, Flemming Besenbacher, Mingdong Dong, Menglin Chen
Among many physical properties, surface nanotopography has been found to strongly affect cell adhesion, migration and other functions. Accurate biological interpretation requires the nanotopography to be presented in a three-dimensional (3D) micro-environment. Herein, immiscible blends of polycaprolactone (PCL)/polyethyleneoxide (PEO) were electrospun into a grounded coagulation bath, resulting in macroporous microfibers with nanotopography featured surfaces. Variations in PCL/PEO ratios enabled tunable surface nanotopographic structures, from longitudinal submicron grooves to transverse nano-lamellae...
July 6, 2017: Nanoscale
Mayur Saxena, Shuaimin Liu, Bo Yang, Cynthia Hajal, Rishita Changede, Junqiang Hu, Haguy Wolfenson, James Hone, Michael P Sheetz
Epidermal growth factor receptor (EGFR) interacts with integrins during cell spreading and motility, but little is known about the role of EGFR in these mechanosensing processes. Here we show, using two different cell lines, that in serum- and EGF-free conditions, EGFR or HER2 activity increase spreading and rigidity-sensing contractions on rigid, but not soft, substrates. Contractions peak after 15-20 min, but diminish by tenfold after 4 h. Addition of EGF at that point increases spreading and contractions, but this can be blocked by myosin-II inhibition...
July 2017: Nature Materials
Jing Yu, Jianyong Huang, John A Jansen, Chunyang Xiong, X Frank Walboomers
Experimental findings indicate that cell function and behavior such as cell growth, division, migration and differentiation, are subtly regulated via integrin-dependent cell adhesion. Cell adhesion is influenced by nanoscale ligand spacing and rigidity of extracellular substrates, as cell adhesion drops greatly when the ligand spacing is larger than ~60nm, and cell adhesion is stronger on stiff than soft substrates. However, how nanoscale ligand spacing and substrate stiffness jointly affect integrin clustering and hence nascent cell adhesion remains to be elucidated...
April 14, 2017: Journal of the Mechanical Behavior of Biomedical Materials
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