Osteopontin (OPN) is an extracellular glycosylated phosphoprotein that promotes cell adhesion by interacting with several integrin receptors. We previously reported that an OPN mutant lacking five O-glycosylation sites (Thr134/Thr138/Thr143/Thr147/Thr152) in the threonine/proline-rich region increased cell adhesion activity and phosphorylation compared with the wild type. However, the role of O-glycosylation in cell adhesion activity and phosphorylation of OPN remains to be clarified. Here, we show that site-specific O-glycosylation in the threonine/proline-rich region of OPN affects its cell adhesion activity and phosphorylation independently and/or synergistically. Using site-directed mutagenesis, we found that OPN mutants with substitution sets of Thr134/Thr138 or Thr143/Thr147/Thr152 had decreased and increased cell adhesion activity, respectively. In contrast, the introduction of a single mutation into the O-glycosylation sites had no effect on OPN cell adhesion activity. An adhesion assay ...
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This application note analyzes the role of different adhesion molecules and chemokines involved in various stages of inflammation under physiological flow conditions. Using Cellixs biochips and Mirus pumping system, THP-1, monocyte and PBMC adhesion to VCAM-1; THP-1, monocyte and PBMC rolling on E-selectin; and respective adhesion blockades is investigated. THP-1 adhesion to HUVECs, correlating adhesion assay results with adhesion molecule expression levels on HUVECs from flow cytometry data, i
Expression of cyclooxygenases (COX) and lipoxygenases (LOX) has been linked to many pathophysiological phenotypes, including cell adhesion. However, many current approaches to measure cellular changes are performed only in a fixed-time point. Since cells dynamically move in conjunction with the cell matrix, there is a pressing need for dynamic or time-dependent methods for the investigation of cell properties. In the presented study, we used stable human colorectal cancer cell lines ectopically expressing COX-1, COX-2, and 15LOX-1, to investigate whether expression of COX-1, COX-2, or 15LOX-1 would affect cell adhesion using our opto-electric methodology. In a fixed-time point experiment, only COX-1- and COX-2-expressing cells enhanced phosphorylation of focal adhesion kinase, but all the transfected cells showed invasion activity. However, in a real-time experiment using opto-electric approaches, transmitted cellular morphology was much different with tight adhesion being shown in COX-2 expressing
The extravasation of leukocytes from the blood into tissues occurs as a multistep process: an initial transient interaction (rolling), generally thought to be mediated by the selectin family of adhesion molecules, followed by firm adhesion, usually mediated by integrins. Using a parallel plate flow chamber designed to approximate physiologic flow in postcapillary venules, we have characterized a rolling interaction between lymphoid cells and adherent primary and cultured endothelial cells that is not selectin mediated. Studies using blocking monoclonal antibodies indicate that this novel interaction is mediated by CD44. Abrogation of the rolling interaction could be specifically achieved using both soluble hyaluronate (HA) and treatment of the adherent cells with HA-reactive substances, indicating that HA is the ligand supporting this rolling interaction. Some B and T cell lines, as well as normal lymphocytes, either constitutively exhibit rolling or can be induced to do so by phorbol ester or ...
Cell adhesion involves receptor-mediated cell-surface interactions with the extracellular matrix (Burridge and Chrzanowska-Wodnicka 1996; Gumbiner 1996). These interactions play a central role in the organization of the cytoskeleton, thereby regulating cell shape and function. Focal adhesions are specialized structures linking the extracellular matrix to the actin microfilaments through integrin and syndecan transmembrane receptors. The structure of the focal adhesion plaque consists of an elaborate network of interconnecting proteins anchoring the microfilaments to the membrane at the contact site. As the points of closest apposition linking the cytoskeleton to the extracellular matrix, focal adhesions are ideally positioned for regulating the adhesive strength of the cell. It may help to think of the cell as having three grades of adhesiveness: (1) weak adherence, meaning that the cell is attached but not spread; (2) intermediate adherence, characterized by a spread cell that lacks stress ...
L-Arginine reduces human monocyte adhesion to endothelial cells and decreases expression of certain endothelial cell adhesion molecules.
The integrin LFA-1 and its ligand ICAM-1 mediate B cell adhesion, but their role in membrane-bound antigen recognition is still unknown. Here, using planar lipid bilayers and cells expressing ICAM-1 fused to green fluorescence protein, we found that the engagement of B cell receptor (BCR) promotes B cell adhesion by an LFA-1-mediated mechanism. LFA-1 is recruited to form a mature B cell synapse segregating into a ring around the BCR. This distribution is maintained over a wide range of BCR/antigen affinities (10(6) M(-1) to 10(11) M(-1)). Furthermore, the LFA-1 binding to ICAM-1 reduces the level of antigen required to form the synapse and trigger a B cell. Thus, LFA-1/ICAM-1 interaction lowers the threshold for B cell activation by promoting B cell adhesion and synapse formation.
The aim of the first part of the thesis was to develop and validate an in vitro adherence assay involving porcine mononuclear cells (MCs) and porcine endothelium, present within gut and lymph node. Factors involved in MC / endothelium interactions were determined. In summary we found that cell adhesion in our assay system was temperature, Ca2+ and Mn2+ sensitive, required metabolic activity, was inhibited by the phosphorylated monosaccharide galactose 6-phosphate, and unaffected by the presence of mucus. These findings reflected certain aspects of in vivo cell adhesion, present within the in vitro assay used. The adhesion characteristics of porcine Peyer s patch (PP), peripheral blood (PB), and lymph node (LN) MCs to porcine gut and lymph node endothelium was examined and used as an guiding model for the future study of human MCs adherence. It was found that PP MCs adhered significantly better to gut endothelium than to LN endothelium and similarly LN MCs adhered significantly better to LN ...
Cell adhesion to extracellular matrix (ECM) is critical to various cellular processes like cell spreading, migration, growth and apoptosis. At the tissue level, cell adhesion is important in the pathological and physiological processes that regulate the tissue morphogenesis. Cell adhesion to the ECM is primarily mediated by the integrin family of receptors. The receptors that are recruited to the surface are reinforced by structural and signaling proteins at the adhesive sites forming focal adhesions that connect the cytoskeleton to further stabilize the adhesions. The functional roles of these focal adhesions extend beyond stabilizing adhesions and transduce mechanical signals at the cell-ECM interface in various signaling events. The objective of this research is to analyze the role of the spatial distribution of the focal adhesions in stabilizing the cell adhesion to the ECM in relation to cells internal force balance. The central hypothesis was that peripheral focal adhesions stabilize cell
Static adhesion of transfectants to immobilized ligands. Adhesion of various integrin transfectants to MAdCAM-1 (top) and ICAM-1 (bottom) was measured in
The modification of medical device surface with adhesive ligands has been recently shown to be an effective means for making a bioselective surface which can inhibit bacterial adhesion while promoting host cell adhesion on device materials. Currently, the lack of quantitative correlation between the adhesion strength of bacteria, nature of adhesive ligand and adhesion kinetics of mammalian cells hinders the development of such device surface. In this study, the biophysical responses of bacteria and mammalian cells towards adhesive ligand on model device surfaces formed by the chemisorption of dopamine (a moderate antibiotic) on glass are elucidated. The effects of RGD, collagen and dopamine modification on the adhesion strength of two clinically significant bacteria including Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were investigated by the determination of minimum lateral forces for bacterial detachment and the density of adhering bacteria. The result indicates that RGD ...
Antioxidants have been proposed to be anti-atherosclerotic agents; however, the mechanisms underlying their beneficial effects are poorly understood. We have examined the effect of alpha-tocopherol (alpha-tcp) on one cellular event in atherosclerotic plaque development, monocyte adhesion to stimulated endothelial cells (ECs). Human umbilical vein ECs were pretreated with alpha-tcp before stimulation with known agonists of monocyte adhesion: IL-1 (10 ng/ml), LPS (10 ng/ml), thrombin (30 U/ml), or PMA (10 nM). Agonist-induced monocytic cell adhesion, but not basal adhesion, was inhibited in a time- and concentration-dependent manner by alpha-tcp. The IC50 of alpha-tcp on an IL-1-induced response was 45 microM. The inhibition correlated with a decrease in steady state levels of E-selectin mRNA and cell surface expression of E-selectin which is consistent with the ability of a monoclonal antibody to E-selectin to inhibit monocytic cell adhesion in this system. Probucol (50 microM) and ...
In the 9 years since the last review on leukocyte and endothelial interactions was published in this journal many of the critical structures involved in leukocyte adherence to and migration across endothelium have been elucidated. With the advent of cell and molecular biology approaches, investigations have progressed from the early descriptions by intravital microscopy and histology, to functional and immunologic characterization of adhesion molecules, and now to the development of genetically deficient animals and the first phase I trial of anti-adhesion therapy in humans. The molecular cloning and definition of the adhesive functions of the leukocyte integrins, endothelial members of the Ig gene superfamily, and the selectins has already provided sufficient information to construct an operative paradigm of the molecular basis of leukocyte emigration. The regulation of these adhesion molecules by chemoattractants, cytokines, or chemokines, and the interrelationships of adhesion pathways need ...
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The integrin subunit beta 1B, a beta 1 isoform with a unique sequence at the cytoplasmic domain, forms heterodimers with integrin alpha chains and binds fibronectin, but it does not localize to focal adhesion sites (Balzac, F., A. Belkin, V. Koteliansky, Y. Balabanow, F. Altruda, L. Silengo, and G. Tarone. 1993. J. Cell Biol. 121:171-178). Here we analyze the functional properties of human beta 1B by expressing it in hamster CHO cells. When stimulated by specific antibodies, beta 1B does not trigger tyrosine phosphorylation of a 125-kD cytosolic protein, an intracellular signalling pathway that is activated both by the endogenous hamster or the transfected human beta 1A. Moreover, expression of beta 1B results in reduced spreading on fibronectin and laminin, but not on vitronectin. Expression of beta 1B also results in severe reduction of cell motility in the Boyden chamber assay. Reduced cell spreading and motility could not be accounted for by preferential association of beta 1B with a given ...
Cell adhesion to the extracellular matrix is required to execute growth factor (GF)-mediated cell behaviors, such as proliferation. A major underlying mechanism is that cell adhesion enhances GF-mediated intracellular signals, such as extracellular signal-regulated kinase (Erk). However, because GFs use distinct mechanisms to activate Ras-Erk signaling, it is unclear whether adhesion-mediated enhancement of Erk signaling is universal to all GFs. We examined this issue by quantifying the dynamics of Erk signaling induced by epidermal growth factor, basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) in NIH-3T3 fibroblasts. Adhesion to fibronectin-coated surfaces enhances Erk signaling elicited by epidermal growth factor but not by bFGF or PDGF. Unexpectedly, adhesion is not always a positive influence on GF-mediated signaling. At critical subsaturating doses of PDGF or bFGF, cell adhesion ablates Erk signaling; that is, adhesion desensitizes the cell to GF ...
Cell adhesion is a fundamental phenomenon vital for all multicellular organisms. Recognition of and adhesion to specific macromolecules is a crucial task of leukocytes to initiate the immune response. To gain statistically reliable information of cell adhesion, large numbers of cells should be measured. However, direct measurement of the adhesion force of single cells is still challenging and todays techniques typically have an extremely low throughput (5-10 cells per day). Here, we introduce a computer controlled micropipette mounted onto a normal inverted microscope for probing single cell interactions with specific macromolecules. We calculated the estimated hydrodynamic lifting force acting on target cells by the numerical simulation of the flow at the micropipette tip. The adhesion force of surface attached cells could be accurately probed by repeating the pick-up process with increasing vacuum applied in the pipette positioned above the cell under investigation. Using the introduced methodology
Hematogenous metastasis requires the arrest and extravasation of blood-borne tumor cells, possibly involving direct adhesive interactions with vascular endothelium. Cytokine activation of cultured human endothelium increases adhesion of melanoma and carcinoma cell lines. An inducible 110-kD endothelial cell surface glycoprotein, designated INCAM-110, appears to mediate adhesion of melanoma cells. In addition, an inducible endothelial receptor for neutrophils, ELAM-1, supports the adhesion of a human colon carcinoma cell line. Thus, activation of vascular endothelium in vivo that results in increased expression of INCAM-110 and ELAM-1 may promote tumor cell adhesion and affect the incidence and distribution of metastases.. ...
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TY - JOUR. T1 - Control of integrin αIIbβ3 outside-in signaling and platelet adhesion by sensing the physical properties of fibrin(ogen) substrates. AU - Podolnikova, Nataly. AU - Yermolenko, Ivan S.. AU - Fuhrmann, Alexander. AU - Lishko, Valeryi K.. AU - Magonov, Sergei. AU - Bowen, Benjamin. AU - Enderlein, Joerg. AU - Podolnikov, Andriy V.. AU - Ros, Robert. AU - Ugarova, Tatiana. PY - 2010/1/12. Y1 - 2010/1/12. N2 - The physical properties of substrates are known to control cell adhesion via integrin-mediated signaling. Fibrin and fibrinogen, the principal components of hemostatic and pathological thrombi, may represent biologically relevant substrates whose variable physical properties control adhesion of leukocytes and platelets. In our previous work, we have shown that binding of fibrinogen to the surface of fibrin clot prevents cell adhesion by creating an antiadhesive fibrinogen layer. Furthermore, fibrinogen immobilized on various surfaces at high density supports weak cell adhesion ...
The broad tissue distribution and evolutionary conservation of the GPI-anchored protein PrP suggests that it plays a role in cellular homeostasis. Since integrin adhesion determines cell behavior, the proposed role of PrP in cell adhesion may underlie the various in vitro and in vivo effects associated to PrP loss-of-function, including the immune phenotypes described in PrP−/- mice. We have investigated the role of PrP in the adhesion and (transendothelial) migration of human (pro)monocytes. We found that PrP regulates β1 integrin-mediated adhesion of monocytes. Additionally, PrP controls cell morphology and migratory behavior of monocytes: PrP-silenced cells show deficient uropod formation on immobilized VCAM and display bleb-like protrusions on the endothelium. Our data further show that PrP regulates ligand-induced integrin activation. Finally, we found that PrP controls the activation of several proteins involved in cell adhesion and migration, including RhoA and its effector cofilin as ...
University of Turku. Professor Johanna Ivaskas (University of Turku) research focus is on the changes that occur in cells with the development of cancer metastases. Integrins are important cell adhesion receptors that regulate the division of cells and their movement in tissue. Changes in cell adhesion properties are a key factor in the formation of cancer metastases. The aim of Professor Ivaskas research is to reach a fundamentally new mechanical understanding of how integrins work in cancer cells and to produce a roadmap of integrin receptor operation and communication chains.. The research combines different methods, including in vivo models, high-throughput screening and applications of synthetic biology. These innovative approaches will yield significant new information about the pathways of cancer cells and their movement in tissue. The project is expected to result in major scientific breakthroughs in this topical field of biomedicine.. Johanna Ivaska is a highly merited researcher. For ...
The idea that cells adhere to one another in a specific manner, such that cells of one type stick only to cells of the same type, appears to have had its origin from the work of Wilson (1907). He found that when cell suspensions from two species of marine sponge were mixed and allowed to aggregate, each individual aggregate body was composed of cells of one species alone. This conclusion has been supported by the results obtained by Humphreys (1963) amongst others, though some workers, who have used different species of sponge, have failed to detect signs of specific adhesion of the cells (Sara, Liaci & Melone, 1966). Until recently there has been little evidence in favour or against the idea that specific adhesion occurs between the cells of higher animals.. ...
Project leader: Prof. Dr. T. Chavakis. Integrin-dependent adhesive interactions between leukocytes and the endothelium contribute to inflammatory processes. In addition, similar adhesive events between haematopoietic stem cells (HSC) and bone marrow stromal cells, including endothelial cells, play a major role for the mobilisation of HSC into peripheral blood and for the homing of HSC to the bone marrow, both processes being relevant for bone marrow transplantation. The beta2-integrin LFA-1, exclusively expressed on cells of haematopoietic origin, is a major adhesion receptor in this context. We recently identified developmental endothelial locus-1 (Del-1 or Edil3), secreted by endothelial cells, as an endogenous inhibitor of LFA-1-dependent leukocyte adhesion to endothelial cells in vitro and leukocyte recruitment in vivo as well as of interleukin-17 (IL-17)-dependent inflammation in the context of aging-associated inflammatory bone loss. Since LFA-1 can regulate adhesive functions of HSC and ...
The invention discloses a cell culture support which provides for the adhesion and culturing of one or more adhesive cells using a photoresist in which to provide a particular patterned design on a surface of the support. The patterned design is provided by the photoresist which is partially removed by photolithography during the making of the support which in turn imparts a striped, checkerboard or dotted pattern on the surface of the support. Further, the cell culture support is produced by pretreating the support surface with a reagent to provide hydrophobicity to the support surface. Also a reagent can be added to pretreat the support surface in order to facilitate adhesion at the photoresist prior to applying the photoresist into the cell culture support. Collagen is applied in the form of a solution, containing in addition thereto albumin and a crosslinking agent, in order to form a film. Collagen specifically affects the cell adhesion rate or the morphology of the cells to be adhered to the
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Cells exert actomyosin contractility and cytoskeleton-dependent force in response to matrix stiffness cues. Cells dynamically adapt to force by modifying their behavior and remodeling their microenvironment. This adaptation is favored by integrin activation switch and their ability to modulate their clustering and the assembly of an intracellular hub in response to force. Indeed integrins are mechanoreceptors and mediate mechanotransduction by transferring forces to specific adhesion proteins into focal adhesions which are sensitive to tension and activate intracellular signals. α(5)β(1) integrin is considered of major importance for the formation of an elaborate meshwork of fibronectin fibrils and for the extracellular matrix deposition and remodeling. Here we summarize recent progress in the study of mechanisms regulating the activation cycle of β(1) integrin and the specificity of α(5)β(1) integrin in mechanotransduction.
Nano-scale or micro-scale adhesive structures comprising an array of nano-fabricated, pillars, the pillars having coated upon, or having disposed on a working surface thereof, a protein-mimetic, marine-adhesive coating. Methods of fabricating the nano-scale pillars, synthesis of the protein-mimetic coating or wet adhesive and application of the adhesive to the pillars are described.
The functionalization of hydrogels for receptor-mediated cell adhesion is one approach for targeted cell and tissue engineering applications. In this study, polyacrylamide gel surfaces were functionalized with specific cell adhesion ligands via the self-assembly of a peptide-based heterodimer. The s …
The CD2 receptor on T lymphocytes is essential for T cell adhesion and stimulation by antigen presenting cells (APCs). Blockade of CD2 function is immunosuppressive in both model systems and humans, indicating the importance of CD2 for the cellular immune response. Although the affinity of the molecular interaction between CD2 and its counter-receptor, CD58, is relatively low when measured in solution, this interaction mediates tight adhesion within the 2D cell-cell interface. To understand the mechanisms responsible for regulating the avidity of the CD2-CD58 interaction, we measured the number, affinity, and lateral mobility of CD2 molecules on resting and activated T cells. Cell activation caused a 1.5-fold increase in the number of CD2 sites on the cell surface, and the 2D affinity of CD2 for CD58 increased by 2.5-fold. The combination of T cell activation and CD2 ligation to CD58 decreased the laterally mobile fraction of the ligated CD2. Together, these changes would substantially enhance CD2
The integrin VLA-3 is a cell surface receptor, which binds to fibronectin, laminin, collagen type I and VI (Takada, Y., E. A. Wayner, W. G. Carter, and M. E. Hemler. 1988. J. Cell. Biochem. 37:385-393) and is highly expressed in substrate adherent cultures of almost all human cell types. The ligand specificity of VLA-3 and the inhibition of cell adhesion by anti-VLA-3 monoclonal antibodies suggest its involvement in cell-substrate interaction. In normal tissues, VLA-3 is restricted to few cell types, notably the kidney glomeruli and basal cells of the epidermis. In the epidermis, VLA-3 is generally strongly expressed on the entire plasma membrane of basal cells and is not polarized towards the basement membrane (Klein, C. E., C. Cardon-Cardo, R. Soehnchen, R. J. Cote, H. F. Oettgen, M. Eisinger, and L. J. Old. 1987. J. Invest. Dermatol. 89:500-507). Based on this finding we speculated that, in addition to a role of VLA-3 for adhesion of cells to substrate, it could also be relevant for cell-cell ...
Colorectal tumors originate and develop within intestinal crypts. Even though some of the essential phenomena that characterize crypt structure and dynamics have been effectively described in the past, the relation between the differentiation process and the overall crypt homeostasis is still partially understood. We here investigate this relation and other important biological phenomena by introducing a novel multiscale model that combines a morphological description of the crypt with a gene regulation model: the emergent dynamical behavior of the underlying gene regulatory network drives cell growth and differentiation processes, linking the two distinct spatio-temporal levels. The model relies on a few a priori assumptions, yet accounting for several key processes related to crypt functioning, such as: dynamic gene activation patterns, stochastic differentiation, signaling pathways ruling cell adhesion properties, cell displacement, cell growth, mitosis, apoptosis and the presence of ...
The role of the mesothelial layer in the peritoneal spreading of cancer cells is only partially clarified. Here we attempted to better define the mesothelial contribution to the tumor cell adhesion using a direct adhesion test applied to human primary cultures of mesothelial cells (HPMCs) derived from the peritoneal washes of patients with gastric and colorectal cancers. Gastric and colon carcinoma cells were seeded on different mesothelial monolayers and quantitative fluorescence analysis was performed to analyze their growth and adhesive properties. The adhesion of the cancer cells was not affected by the origin of the HPMCs when derived from patients with different cancers or with benign disease. In contrast, the high levels of ICAM1 expression and ROS production, which characterize these senescent mesothelial cells, enhanced the tumor cell adhesion. These results suggest that the mesothelial adhesive properties are dependent on the cell senescence, while are not affected by the tumor ...
My recent research has focused on how leukocytes control their adhesiveness and has resulted in a discovery of a novel regulatory pathway, Rogelj relates. Its a Rube Goldberg kind of sequence: Biochemical events that occur along this pathway determine the expression of a critical cell surface adhesion molecule, which in turn determines the ability of a leukocyte to recognize its target. Signals that lead to a loss of cell adhesiveness, therefore, result in suppression of the immune response. And, suppression of the immune system may or may not be a good thing ...
Our laboratory consists of 5 Research Fellows and a Junior Faculty member who are physician scientists or research scientists and two senior research technicians. who use a combination of immunological, biochemical and molecular biological strategies to study leukocyte recruitment in various in vitro and in vivo models of inflammation. We have developed a valuable in vitro model that allows direct microscopic examination of live leukocyte Ð endothelial interactions under defined laminar fluid shear stress conditions that mimic blood flow in small venules. Areas of focus using this model are three-fold: first, dissection of the adhesion mechanisms that support blood monocyte and specific T cell subset adhesive interactions with endothelium under flow, or specific recombinant endothelial cell adhesion molecules; second, characterization of endothelial-dependent mechanisms involved in regulation of endothelial cell borders (lateral junctions) during leukocyte transmigration, permeability function ...
The Ly-6 locus on mouse chromosome 15 encodes a family of 10-12 kDa proteins that are linked to the cell surface by a glycosylphosphatidyl-inositol anchor and have cell signaling and cell adhesion properties. Expression of Ly-6 proteins is tightly regulated during development; these proteins continu.... Full description. ...
The leukocyte adhesion cascade is an important paradigm of immunity and mediates leukocyte recruitment in acute or chronic inflammatory responses. Leukocyte recruitment requires several adhesive interactions between leukocytes and endothelial cells. The adhesion of leukocytes to the endothelial cell surface is mediated by interactions between leukocyte integrins, such as the beta1-integrin family member VLA-4 (a4b1) or the beta2-integrin family members LFA-1 (aLb2, CD11a/CD18), Mac-1 (aMb2, CD11b/CD18, complement receptor-3), and their endothelial counter-receptors of the immunoglobulin superfamily (ICAM-1, VCAM-1) (1). Our lab has made significant contributions to the leukocyte adhesion cascade, including the recent identification of a novel endogenous inhibitor of leukocyte recruitment, the endothelial-derived molecule Developmental Endothelial Locus-1 (Del-1, Edil3) (2-4).. Mobilization of hematopoietic stem cells (HSC) from the bone marrow to the periphery takes place upon infection. HSC ...
Prostate Cancer (PCa) is the second leading cause of cancer death in American men.. The inflammatory tumor microenvironment is a fertile niche that releases reactive oxygen species, which accelerates the malignant transformation and appears as a fine tuner of the adhesive behavior of cells. Heme oxygenase 1 (HO-1), the rate-limiting enzyme in heme degradation, represents an essential event in cellular responses to pro-oxidative and pro-inflammatory insults. As we previously reported that HO-1 over-expression impaired tumor growth and angiogenesis in vivo we sought to assess whether HO-1 could regulate the adhesive properties and the morphology of PCa cells. A bioinformatics enrichment analysis using Metacore, GeneMANIA and DAVID was performed; rendering a significant association of the HO-1 regulated genes with several proteins located in the extracellular space and cell membrane; compartments highly correlated with the adhesive behavior of cells. In an effort to understand the molecular ...
Effect of Ni addition on the microstructures of melt-spun CuCr ribbons. YU, M.; WANGI, Y.; WANG, Y.; SUN, Z. // Materials Science (0137-1339);2008, Vol. 26 Issue 3, p675 The microstructures and resistivities of melt-spun Cu75Cr25 and Cu(75-x)Cr25Nix (x = 1 or 3 wt. %) ribbons were studied. The size of the Cr-rich phase from liquid phase separation in the Cu75Cr25 microstructure can be decreased from the micrometer-scale to about 250 nm by using melt spinning.... ...
Sample preparation has always been a notoriously time consuming task that tends to detract from the more essential functions of collecting and analyzing data. A few key factors come in to play with improving the process of plating cells for imaging and the time that it takes. Cell adhesion, media re-equilibration, an unobstructed path for free migration of cells are some of the important factors to improve plating efficiency. Cell adhesion is pendant on the surface the cells are being plated on. The chemical composition of the glass affects cell adhesion and all glass surfaces are not created equal. It is best to use glass that is alkaline free and designed for cell adhesion (check out the Bioptechs Delta T Culture Dishes, FCS2 coverslips, 30mm ICD coverslips, and Microaquaduct slides). Sometimes an ECM is required depending on the cell type and protocol, however, in all cases cell plating is improved with the use of Culture Cylinders. A unique attribute of using a Culture Cylinder for plating ...
Here, we investigated molecular and biophysical mechanisms through which GBM cells adhere to HA matrix. We find that GBM cells interact with HA via McTNs, which are long, thin protrusions rich in the HA receptor CD44, which we show is necessary for cell adhesion and McTN stability. Motility assays and laser ablation indicate that McTNs are stabilized by a balance of actomyosin-driven contraction, microtubule-driven protrusion, and CD44-mediated adhesion. Mechanical coupling of actin and microtubules with McTNs appears to be reinforced by a complex of IQGAP1 and CLIP170, and loss of IQGAP1 specifically disrupts adhesion and motility on HA.. McTNs, which can be functionally defined as microtubule-positive protrusions that elongate following actin depolymerization, have been observed in circulating tumor cells (CTCs), where they are believed to facilitate endothelial adhesion prior to extravasation (30⇓-32). However, to our knowledge, these structures have not been previously appreciated in the ...
Cell adhesion to the extracellular matrix (ECM) is necessary for fundamental cellular processes such as survival, migration, and differentiation. Adhesion is mediated by integrin receptors, which recruit multiprotein adhesion complexes to sites of attachment to the ECM. Adhesion complexes provide a structural connection between the ECM and cytoskeleton, transmit mechanical force, and act as signaling hubs to control cell behavior. Recent high-resolution imaging studies of adhesion sites reveal some aspects of their spatial organization and provide insights into their function at the molecular level.. ...
In this study, we have investigated whether SHIP plays a role in PMA- or cytokine-mediated LFA-1 activation by overexpressing both WT and phosphatase dead forms of SHIP in DA-ER cells. Our results show that 1) overexpression of WT-SHIP in unstimulated DA-ER cells increases LFA-1-mediated cell adhesion to ICAM-1, and this adhesion is further augmented by the addition of PMA, IL-3, or Epo; 2) SHIP requires a functional 5′-phosphatase domain for these effects, and overexpression of a phosphatase dead form actually leads to a slight inhibition of LFA-1-mediated adhesion to ICAM-1; 3) SHIP overexpression most likely enhances adhesion via its effect on inside-out signaling because its overexpression has no effect on the external activation of LFA-1 by Mn2+; 4) LFA-1 activation on cells overexpressing WT-SHIP does not involve activation of Erk-1 and Erk-2; and 5) LFA-1 activation in response to PMA in SHIP-overexpressing cells is via its effects on a PKC-stimulated pathway, while LFA-1 activation in ...
We have designed a lightly crosslinked PEG based copolymer coating with compositional flexibility as well as extended stability for studying human mesenchymal stem cells (hMSCs). Copolymers contain a majority of poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) as a cytophobic background with poly(et
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A diverse family of cell surface and extracellular glycoproteins involved in cell-cell adhesion, cell-extracellular matrix adhesion, recognition, and activation. There are four main classes of cell adhesion molecules: integrins, selectins, cadherins, and immunoglobulin-like adhesion molecules. [National Cancer Institute Thesaurus].. ...
Definition of Leukocyte-endothelial cell adhesion molecule 1 in the Legal Dictionary - by Free online English dictionary and encyclopedia. What is Leukocyte-endothelial cell adhesion molecule 1? Meaning of Leukocyte-endothelial cell adhesion molecule 1 as a legal term. What does Leukocyte-endothelial cell adhesion molecule 1 mean in law?
TY - JOUR. T1 - Growth cone interactions with purified cell and substrate adhesion molecules visualized by interference reflection microscopy. AU - Drazba, Judith. AU - Liljelund, Patricia. AU - Smith, Carolyn. AU - Payne, Ross. AU - Lemmon, Vance. PY - 1997/6/18. Y1 - 1997/6/18. N2 - The migration of growth cones on substrates consisting of naturally occurring cell adhesion molecules has been extensively studied in cell culture. However, relatively little is known about how growth cones contact the substrate or how the patterns of contact change as growth cones move forward. We have examined the interactions of chick retinal ganglion cell growth cones with laminin, merosin, N-cadherin, L1 and poly-L-lysine by time- lapse interference reflection microscopy (IRM) using a laser scanning confocal microscope. In images obtained by IRM, areas of a cell that are closely apposed to the substrate appear dark whereas areas that are farther away appear light. Growth cones on laminin and merosin were ...
TY - JOUR. T1 - Thrombin-mediated Focal Adhesion Plaque Reorganization in Endothelium. T2 - Role of Protein Phosphorylation. AU - Schaphorst, Kane L.. AU - Pavalko, Frederick M.. AU - Patterson, Carolyn E.. AU - Garcia, Joe G.N.. PY - 1997/1/1. Y1 - 1997/1/1. N2 - Endothelial cell (EC) gap formation and barrier function are subject to dual regulation by (1) axial contractile forces, regulated by myosin light chain kinase activity, and (2) tethering forces, represented by cell-cell and cell-substratum adhesions. We examined whether focal adhesion plaque proteins (vinculin and talin) and focal adhesion kinase, p125FAK (FAK), represent target regulatory sites involved in thrombin-mediated EC barrier dysfunction. Histologically, thrombin produced dramatic rearrangement of EC actin, vinculin, and FAK in parallel with the evolution of gap formation and barrier dysfunction. Vinculin and talin were in vitro substrates for phosphorylation by EC PKC, a key effector enzyme involved in thrombin-induced EC ...
Background: Mast cells infiltrate the bronchial smooth muscle (BSM) in asthmatic patients, but the mechanism of mast cell adhesion is still unknown. The adhesion molecules CD44 (i.e. hyaluronate receptor) and CD51 (i.e. vitronectin receptor) are widely expressed and bind to many extracellular matrix (ECM) proteins. The aims of the study are (i) to identify the role of ECM in mast cell adhesion to BSM and (ii) to examine the role of CD51 and CD44 in this adhesion.. Methods: Human lung mast cells, human mast cell line (HMC-1), and BSM cells from control donors or asthmatic patients were cultured in the presence/absence of various cytokines. Mast cell-BSM interaction was assessed using 3H-thymidine-pulsed mast cells, confocal immunofluorescence, or electron microscopy. Adhesion molecules expression and collagen production on both cell types were evaluated by quantitative RT-PCR, western blot, and flow cytometry.. Results: Mast cell adhesion to BSM cells mostly involved type I collagen of the ECM. ...
CD2 is a T lymphocyte glycoprotein that functions in adhesion of T lymphocytes and also as a putative receptor for activation signals. Functional data suggest that LFA-3, a widely distributed cell surface glycoprotein, may be the biological ligand of CD2. We have purified LFA-3 from human erythrocytes and characterized the purified protein functionally. LFA-3 bound specifically to CD2+ cells, and this binding was inhibited by CD2 mAb. Conversely, purified LFA-3 inhibited binding of CD2 mAb to cells, and the concentration required for this effect suggests that LFA-3 half-saturated CD2 at 1-5 nM LFA-3. Purified LFA-3 inhibited rosetting of human and sheep erythrocytes with CD2+ T lymphoma cells and T lymphocytes, and mediated aggregation of a CD2+ T lymphoma cell line. Purified LFA-3 reconstituted into planar membranes mediated efficient CD2-dependent adhesion of T lymphoblasts. These data demonstrate that LFA-3 is a ligand for CD2 and that LFA-3 can mediate T lymphocyte adhesion.
TY - JOUR. T1 - An equilibrium model of endothelial cell adhesion via integrin-dependent and integrin-independent ligands. AU - Chan, Bernard P.. AU - Bhat, Vinayak D.. AU - Yegnasubramanian, Srinivasan. AU - Reichert, William M.. AU - Truskey, George A.. PY - 1999/12/1. Y1 - 1999/12/1. N2 - Endothelial cell adhesion can be enhanced by supplementing integrin-mediated adhesion via fibronectin with the high-affinity avidin-biotin system in which biotin is covalently linked to membrane proteins and avidin binds to biotinylated surfaces (Bhat et al. J Biomed Mater Res 1998;41:377-85). An equilibrium model was extended to explain detachment of spreading cells following exposure to flow for this two ligand system. The two different receptor-ligand systems were treated as springs in parallel in which the equilibrium dissociation constant was a function of the separation distance of the cell from the surface. Flow experiments were performed to measure the endothelial cell adhesion strength as a function ...
TY - JOUR. T1 - Dynamic control of cell adhesion on a stiffness-tunable substrate for analyzing the mechanobiology of collective cell migration. AU - Kamimura, Masao. AU - Sugawara, Michiko. AU - Yamamoto, Shota. AU - Yamaguchi, Kazuo. AU - Nakanishi, Jun. N1 - Publisher Copyright: © 2016 The Royal Society of Chemistry. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 2016/6. Y1 - 2016/6. N2 - A method was developed for photocontrolling cell adhesion on a gel substrate with defined mechanical properties. Precise patterning of geometrically controlled cell clusters and their migration induction became possible by spatiotemporally controlled photo-irradiation of the substrate. The clusters exhibited unique collective motion that depended on substrate stiffness and cluster geometry.. AB - A method was developed for photocontrolling cell adhesion on a gel substrate with defined mechanical properties. Precise patterning of geometrically controlled cell clusters and their migration ...
We have distinguished five TNF-alpha-inducible cell adhesion mechanisms on microvasculature-derived endothelioma cells of the mouse which mediate the binding of different types of leukocytes. Three of these mechanisms could be identified as the mouse homologs of ICAM-1, VCAM-1, and E-selectin, of which the latter was defined by the novel mAb 21KC10. The fourth TNF-alpha-inducible cell adhesion mechanism was blocked by antibodies specific for mouse P-selectin. We have recently shown that TNF-alpha stimulates the synthesis of P-selectin in mouse endothelioma cells (A. Weller, S. Isenmann, D. Vestweber. 1992. J. Biol. Chem. 267:15176-15183). Here we show that this stimulation leads to maximal cell surface expression levels within 4 h after stimulation while the same endothelioma cells are also able to upregulate P-selectin at the cell surface within minutes after stimulation with PMA. Both effects are additive. The fifth TNF-induced cell adhesion mechanism is defined by mediating the binding to the ...
alpha 4 integrins are cell surface receptors that mediate cell-extracellular matrix (ECM) and cell-cell adhesions by interacting with fibronectin (FN) and vascular cell adhesion molecule 1 (VCAM-1), respectively. We have generated a null mutation in the gene for the alpha 4 integrin subunit. Homozygous null embryos express no alpha 4 integrins and show two unexpected defects, both of which lead to embryonic lethality. The first defect is failure of fusion of the allantois with the chorion during placentation. The second is in the development of the epicardium and coronary vessels leading to cardiac hemorrhage. Both processes clearly involve alpha 4 integrin interactions that were previously unsuspected. alpha 4 integrin and VCAM-1 are expressed at the sites of these interactions. These results raise the possibility of abortifacients targeting alpha 4 integrins, and raise serious questions about potential side effects of drugs currently being designed to block alpha 4 integrin functions in ...
This study presents the comparative cell attachment investigation of TAT and well-known RGD peptide modified surfaces. Initially, cysteine containing arginine-glycine-aspartic acid (RGD) and TAT peptides, a class of cell penetration peptides, were synthesized. Gold film coated indium tin oxide (gold/ITO) surfaces were coated with RGD and TAT peptides and used for cell culture applications. Thiol groups on the peptides provide post-modification of the surface. The efficient bonding of the peptides with the modified surface brings proper attachment of the cells. The peptide modified surfaces were tested for adhesion of several cell lines such as monkey kidney epithelial cell (Vero), human cervical carcinoma cell (HeLa), human glioblastoma cell (U87-MG) and human immortalized skin keratinocyte cell (HaCaT) lines. These cells were cultured on RGD and TAT modified gold/ITO surfaces. Cell imaging studies were performed on these surfaces using fluorescence microscopy technique. Scanning electron ...
TY - CHAP. T1 - Laser Surface Engineering of Polymeric Materials for Enhanced Mesenchymal Stem Cell Adhesion and Growth. AU - Waugh, David. AU - Cosgrove, Daniel. AU - Hussain, Issam. AU - Lawrence, Jonathan. PY - 2019/5/3. Y1 - 2019/5/3. N2 - Owing to them being relatively inexpensive and easy to manipulate, polymers are becoming more widely used within the biomedical industry for several different applications. As an example, because of its high wear resistance, low moisture absorption and high chemical resistance, poly(ether ether ketone) is commonly used as a biomaterial in the healthcare and biomedical industries. However, poly(ether ether ketone) surface properties are not optimum for efficient or enhanced bio-functionality, leading it to have somewhat inferior wettability and adhesion characteristics. On account of this, many researchers are now looking to employ surface engineering techniques to improve and enhance the surface properties of poly(ether ether ketone), enhancing its ...
TY - JOUR. T1 - Localized zones of Rho and Rac activities drive initiation and expansion of epithelial cell-cell adhesion. AU - Yamada, Soichiro. AU - Nelson, W. James. PY - 2007/7/30. Y1 - 2007/7/30. N2 - Spatiotemporal coordination of cell-cell adhesion involving lamellipodial interactions, cadherin engagement, and the lateral expansion of the contact is poorly understood. Using high-resolution live-cell imaging, biosensors, and small molecule inhibitors, we investigate how Rac1 and RhoA regulate actin dynamics during de novo contact formation between pairs of epithelial cells. Active Rac1, the Arp2/3 complex, and lamellipodia are initially localized to de novo contacts but rapidly diminish as E-cadherin accumulates; further rounds of activation and down-regulation of Rac1 and Arp2/3 occur at the contacting membrane periphery, and this cycle repeats as a restricted membrane zone that moves outward with the expanding contact. The cortical bundle of actin filaments dissolves beneath the ...
Cell-matrix and cell-cell adhesions are often characterized as functionally distinct adhesion systems within the cell that mediate different proliferative outcomes. In contrast to the widely accepted pro-proliferative effect of cell-matrix adhesion, the proliferative effect of cadherin-dependent cell-cell adhesion remains unresolved. While the majority of studies demonstrate that cadherins mediate contact inhibition of proliferation, there have also been compelling reports of cadherins stimulating cell cycling. Here, we show that matrix stiffness is the mechanistic basis for crosstalk between N-cadherin at cell-cell junctions and focal adhesion kinase (FAK) at cell-matrix adhesions, and that this interplay between adhesive systems modulates the proliferative role of N-cadherin. We demonstrate that N-cadherin is induced in smooth muscle cells (SMCs) following vascular injury, an in vivo model of tissue stiffening and proliferation. Complementary experiments on deformable polyacrylamide hydrogels
Definition of Cell adhesion molecule in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is Cell adhesion molecule? Meaning of Cell adhesion molecule as a finance term. What does Cell adhesion molecule mean in finance?
Tumor cells that acquire metastatic potential have developed resistance to anoikis, a cell death process, after detachment from their primary site to the second organ. In this study, we investigated the molecular mechanisms of a novel marine bacterial polysaccharide EPS11 which exerts its cytotoxic effects through affecting cancer cell adhesion and anoikis. Firstly, we found that EPS11 could significantly affect cell proliferation and block cell adhesion in A549 cells. We further demonstrated that the expression of several cell adhesion associated proteins is downregulated and the filiform structures of cancer cells are destroyed after EPS11 treatment. Interestingly, the destruction of filiform structures in A549 cells by EPS11 is in a dose-dependent manner, and the inhibitory tendency is very consistent with that observed in the cell adhesion assay, which confirms that filiform structures play important roles in modulating cell adhesion. Moreover, we showed that EPS11 induces apoptosis of A549 ...
TY - CHAP. T1 - Biophysics of selectin-mediated cell adhesion. AU - Cheung, L. S.L.. AU - Raman, P. S.. AU - Wirtz, D.. AU - Konstantopoulos, K.. PY - 2012/12/1. Y1 - 2012/12/1. N2 - Selectins (L-, P- and E-selectin) are Ca2+-dependent transmembrane glycoproteins presented on the surface of circulating leukocytes, activated platelets, and endothelial cells at sites of inflammation/infection. Selectins bind primarily to sialofucosylated glycoproteins and glycolipids (E-selectin only) on apposing cells, and mediate loose adhesive interactions pertinent to inflammatory disorders and blood-borne metastasis. The fast association and dissociation rates of selectin-ligand bonds coupled to their remarkably high tensile strengths enable them to initiate cell tethering and rolling interactions under physiological flow conditions. This chapter reviews mathematical models and experimental methodologies to highlight the biophysics of selectin-mediated cell adhesion. It summarizes experimental observations on ...
Mammalian cells dynamically interact with the surrounding microenvironments through cell surface molecules. This dynamic interaction is crucial in many processes from wound healing, immune cell infiltration to cancer invasion. Two important classes of cell surface receptors that mediate cell-matrix and cell-cell adhesions are integrins and cadherins, respectively. They are assembled into large adhesion complexes (integrin-based focal adhesions and cadherin-based adherens junctions) and via actin-binding proteins play an important role in mechanical coupling the cell to other cells as well to the extracellular matrix (ECM). Besides providing an important structural basis for anchoring the actin cytoskeleton to the plasma membrane, these adhesive structures can also influence signaling events that control important cellular processes, such as cell survival, proliferation and differentiation. Genetic defects in critical components of the cell adhesion junctions are part of various rare diseases. ...
Matrix-activated integrins can form different adhesion structures. We report that nontransformed fibroblasts develop podosome-like adhesions when spread on fluid Arg-Gly-Asp peptide (RGD)-lipid surfaces, whereas they habitually form focal adhesions on rigid RGD glass surfaces. Similar to classic macrophage podosomes, the podosome-like adhesions are protrusive and characterized by doughnut-shaped RGD rings that surround characteristic core components including F-actin, N-WASP, and Arp2/Arp3. Furthermore, there are 18 podosome markers in these adhesions, though they lack matrix metalloproteinases that characterize invadopodia and podosomes of Src-transformed cells. When nontransformed cells develop force on integrin-RGD clusters by pulling RGD lipids to prefabricated rigid barriers (metal lines spaced by 1-2 μm), these podosomes fail to form and instead form focal adhesions. The formation of podosomes on fluid surfaces is mediated by local activation of phosphoinositide 3-kinase (PI3K) and the ...
TY - JOUR. T1 - Adhesion Characteristics of Murine Metastatic and Nonmetastatic Tumor Cells in Vitro. AU - Murray, J. Clifford. AU - Liotta, Lance. AU - Rennard, Stephen I.. AU - Martin, George R.. PY - 1980/2/1. Y1 - 1980/2/1. N2 - We have studied the attachment of mouse fibroblasts, transformed nonmetastatic fibroblasts, and metastatic fibrosarcoma cells to various substrates. The metastatic cells attach preferentially to type IV (basement membrane) collagen in the absence of serum, compared to type I collagen and plastic. In the presence of fibronectin, these cells attach well to both type I and type IV collagens. The normal and transformed fibroblasts attach to all these substrates, although the transformed fibroblasts attach more slowly. The ability to attach to type I collagen and plastic is correlated with the levels of fibronectin and collagen produced by these cells. The data indicate that the transformed and metastatic cells differ from normal cells in their attachment properties and ...
TY - JOUR. T1 - Similarities between heterophilic and homophilic cadherin adhesion. AU - Prakasam, A. K.. AU - Maruthamuthu, V.. AU - Leckband, D. E.. PY - 2006/10/17. Y1 - 2006/10/17. N2 - The mechanism that drives the segregation of cells into tissue-specific subpopulations during development is largely attributed to differences in intercellular adhesion. This process requires the cadherin family of calcium-dependent glycoproteins. A widely held view is that protein-level discrimination between different cadherins on cell surfaces drives this sorting process. Despite this postulated molecular selectivity, adhesion selectivity has not been quantitatively verified at the protein level. In this work, molecular force measurements and bead aggregation assays tested whether differences in cadherin bond strengths could account for cell sorting in vivo and in vitro. Studies were conducted with chicken N-cadherin, canine E-cadherin, and Xenopus C-cadherin. Both qualitative bead aggregation and ...
To investigate the effect of PICSAR on cell spreading, PICSAR overexpressing cells were plated on collagen I and fibronectin. PICSAR overexpression resulted in impaired cell spreading and the relative number of spread cells was significantly decreased in PICSAR overexpressing cells compared to control cells (Fig. 3C). Immunofluorescence staining revealed expression of α2 and α5 integrins in PICSAR overexpressing cSCC cells plated on collagen I and fibronectin, but compared to the control cells there were no clear adhesion sites in PICSAR overexpressing cells, likely due to decreased cell spreading (Fig. 3D). In accordance with this, real-time cell adhesion assay revealed decreased adhesion of PICSAR overexpressing cSCC cells on collagen I and fibronectin, as compared to control cells (Fig. 3E). Furthermore, migration of PICSAR overexpressing cSCC cells in wound healing assay was increased compared to control cells (Fig. 3F). These results show for the first time a functional link between a ...
Assays using purified proteins under flow and cells under static conditions were used to evaluate the inhibitory activity of this compound in vitro. Biacore analysis demonstrated that PSI-697 effectively inhibited binding of P-selectin to PSGL-1 with 50% inhibition of binding at 125 μM. A 2-fold lower inhibitory concentration of PSI-697 was observed when PSGL-1-expressing cells were subjected to a static adhesion assay. This high concentration in vitro and difference between the monomeric protein/protein interactions of the Biacore assay and multimeric cell/protein interaction of the static cell assay probably reflect the difficulty in reproducing in vivo flow rates, selectin densities, and other contributing cellular interactions in vitro. It suggests that in vivo receptor occupancy requirements may be lower than those in vitro, and as expected for a flow-dependent interaction, the EC50 of PSI-697 decreased further from the Biacore and static adhesion assay to the in vivo models described ...
Adhesion characteristics of copper thin film deposited on PET substrate by electron cyclotron resonance-metal organic chemical vapor deposition ...
Neutrophil invasion of inflamed tissue is a complex process involving an initial mild adhesive interaction with the venular endothelium, termed rolling, which allows neutrophils to remain in close apposition to the endothelial cells and to sample the environment for local signals of an ongoing inflammatory process.1 2 3 If the appropriate signals (stimuli) are present, the neutrophils become activated, and a strong adhesive interaction takes place. This results in neutrophil arrest and eventual emigration toward the chemotactic stimulus in the interstitium. Although there is a general consensus on the mechanisms (adhesion molecule activation/expression) involved in neutrophil-endothelial cell adhesive interactions,1 2 3 the mechanisms by which neutrophils penetrate the endothelial cell lining to gain access to the interstitium remain controversial. The barriers to neutrophil movement to the site of chemotactic (or inflammatory) stimuli in the interstitium are (1) the endothelial cells lining the ...
Cell adhesion molecules are cell surface glycoproteins, the function of which is regulated by neurons at different stages of brain development and in response to a variety of external stimuli, for example during learning.. This project will aim to identify and characterise new endogenous regulators of cell adhesion molecules and test artificial regulators of cell adhesion molecules to analyse their pharmacological potential in various disease models.Recombinant protein production, mass spectrometry, protein-protein interaction assays, various protein analysis tools, and cellular models will be used.. ...
TY - JOUR. T1 - Enhanced cell adhesion and mature intracellular structure promoted by squaramide-based RGD mimics on bioinert surfaces. AU - Narasimhan, Sri Kamesh. AU - Sejwal, Preeti. AU - Zhu, Shifa. AU - Luk, Yan Yeung. PY - 2013/4/15. Y1 - 2013/4/15. N2 - Highly selective molecular binding and the subsequent dynamic protein assemblies control the adhesion of mammalian cells. Molecules that inhibit cell adhesion have the therapeutic potential for a wide range of diseases. Here, we report an efficient synthesis (2-4 steps) of a class of squaramide molecules that mimics the natural tripeptide ligand Arg-Gly-Asp (RGD) that mediates mammalian cell adhesion through binding with membrane protein integrin. In solution, this class of squaramides exhibits a higher potency at inhibiting mammalian cell adhesion than RGD tripeptides. When immobilized on a bio-inert background formed by self-assembled monolayers of alkanethiols on gold films, squaramide ligands mediate vastly different intracellular ...
Fingerprint Dive into the research topics of Mimicking filtration and transport of rotavirus and adenovirus in sand media using DNA-labeled, protein-coated silica nanoparticles. Together they form a unique fingerprint. ...
Berkenhoff, Kristine (2013): Subcutaneous suspensions of therapeutic proteins formulated as protein-coated microcrystals. Dissertation, LMU München: Faculty of Chemistry and Pharmacy ...
Dysfunction of cell adhesion occurs during cancer metastasis. Loss of cell-cell adhesion in metastatic tumour cells allows them to escape their site of origin and spread through the circulatory system.[5] One example of CAMs deregulated in cancer are cadherins, which are inactivated either by genetic mutations or by other oncogenic signalling molecules, allowing cancer cells to migrate and be more invasive.[6] Other CAMs, like selectins and integrins, can facilitate metastasis by mediating cell-cell interactions between migrating metastatic tumour cells in the circulatory system with endothelial cells of other distant tissues.[35] Due to the link between CAMs and cancer metastasis, these molecules could be potential therapeutic targets for cancer treatment. There are also other human genetic diseases caused by an inability to express specific adhesion molecules. An example is leukocyte adhesion deficiency-I (LAD-I), where expression of the β2 integrin subunit is reduced or lost.[36] This leads ...
Background: Neopetrosiamide A (NeoA) is a 28-amino acid tricyclic peptide originally isolated from a marine sponge as a tumor cell invasion inhibitor whose mechanism of action is unknown. Methodology/Principal Findings: We show that NeoA reversibly inhibits tumor cell adhesion, disassembles focal adhesions in pre-attached cells, and decreases the level of beta 1 integrin subunits on the cell surface. NeoA also induces the formation of dynamic, membrane-bound protrusions on the surface of treated cells and the release of membrane-bound vesicles into the culture medium. Proteomic analysis indicates that the vesicles contain EGF and transferrin receptors as well as a number of proteins involved in adhesion and migration including: beta 1 integrin and numerous alpha integrin subunits; actin and actin-binding proteins such as cofilin, moesin and myosin 1C; and membrane modulating eps15 homology domain (EHD) proteins. Surface labeling, trafficking inhibition, and real-time imaging experiments all ...
Cadherins are transmembrane glycoproteins vital in calcium-dependent cell-cell adhesion during tissue differentiation. Cadherins cluster to form foci of homophilic binding units. A key determinant to the strength of the cadherin-mediated adhesion may be by the juxtamembrane region in cadherins. This region induces clus
Discoid red blood cells (RBCs) deposited irreversibly on a horizontal glass surface are studied by means of optical microscopy and image analysis. The relative surface covered by the RBCs, as well as the variance of this surface coverage as a functio
By Ramis-Conde, Ignacio Drasdo, Dirk; Anderson, Alexander R A; Chaplain, Mark A J ABSTRACT In this article, we show, using a mathematical multiscale model, how cell adhesion may be regulated by interactions between E-cadherin and beta-catenin and how the control of cell adhesion may be related to cell migration, to the epithelial- mesenchymal transition and to invasion in populations of eukaryotic cells. E-cadherin mediates cell-cell adhesion and plays a critical role in the formation and maintenance of junctional contacts between cells. Loss of E-cadherin-mediated adhesion is a key feature of the epithelial-mesenchymal transition. beta-catenin is an intracellular protein associated with the actin cytoskeleton of a cell. E- cadherins bind to beta-catenin to form a complex which can interact both with neighboring cells to form bonds, and with the cytoskeleton of the cell. When cells detach from one another, beta-catenin is released into the cytoplasm, targeted for degradation, and downregulated. ...
Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here. ...
The RGD peptide is the binding motif of fibronectin to cell adhesion molecules. RGD peptide acts as an inhibitor of integrin-ligand interactions and can induce apoptosis in the absence of signals and integrin-mediated cell clustering. Research demonstrates that RGD peptides promote apoptosis through activation of conformation changes that enhance pro-caspase-3 activation and autoprocessing. The RGD peptide can serve as a cell adhesion site of extracellular matrix, cell surface proteins, and integrins. In addition, RGD peptide can inhibit ACK-2 activation through cell adhesion. ...
A foam substrate-attached adhesive sheet or tape comprising a substrate having formed thereon a layer of a pressure-sensitive adhesive, wherein the substrate is a foam elastomer having a breaking elongation of at least 800% and an apparent 800% modulus of from 1.0 to 15 kg/cm2 in a tensile test of 23 C., and a breaking elongation of at least 400% and an apparent 400% modulus of from 2.0 to 60 kg/cm2 in a tensile test of -30 C.
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Clone REA697 recognizes the rat CD146 (LSEC) antigen, also known as Gicerin, MCAM, MUC18, or MEL-CAM. CD146 is a putative cell adhesion molecule of an immunoglobulin (Ig) superfamily which shows homophilic and heterophilic binding activities with two isoforms: S-gicerin, which has small cytoplasmic domain and the same extracellular domain as l-gicerin, shows stronger cell adhesion activity. CD146 is expressed on endothelial cells and a variety of tumor cells and is involved in cell adhesion and in cohesion of the endothelial monolayer at intercellular junctions in vascular tissue. In rat, neurite promotion activity of CD146 from hippocampal neurons is reported. Additional information: Clone REA697 displays negligible binding to Fc receptors. - Belgique
1166 Tumor cell metastasis is a complex, multi-step process that is a major cause of morbidity and death amongst cancer patients. Cell adhesion plays a critical role in the development of metastatic cancer, and it is mediated by interactions between receptors on the cell surface and ligands of the extracellular matrix or other surfaces. Therefore, inhibition of the cell adhesion process appears to be an effective method of preventing metastasis. To prevent cell adhesion, we developed genetically engineered polypeptides with the potential to inhibit metastases. We have found that the cell penetrating peptides (CPP) Tat or penetratin (Pen), fused with elastin-like polypeptide (CPP-ELP) inhibited adhesion, spreading, invasion and migration of SKOV-3 ovarian cancer cells, SK-MEL-2 melanoma cells, and MDA-MB-231 breast cancer cells in cell culture. Furthermore, we have also confirmed that Tat-ELP has anti-metastatic potential in an experimental ovarian cancer metastasis model in vivo. Therefore, ...
Organic coatings adhere better to polyester film base if the film base is first subjected to electron-beam irradiation while passing through an inert atmosphere such as nitrogen.
This gene is a type II classical cadherin from the cadherin superfamily and one of three cadherin 7-like genes located in a cluster on chromosome 18. The encoded membrane protein is a calcium dependent cell-cell adhesion glycoprotein comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. Since disturbance of intracellular adhesion is a prerequisite for invasion and metastasis of tumor cells, cadherins are considered prime candidates for tumor suppressor genes.