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Dissertations / Theses on the topic 'Molecular adhesion'
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Townsend, Paul Andrew. "The molecular basis of osteoblast adhesion." Thesis, University College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263651.
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Lougheed, Caroline. "Targeting focal adhesion signaling in cancer and acquired resistance to focal adhesion kinase inhibitors." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=94996.
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In cancer progression, the development of metastases is characteristic of late stage disease and makes treatment and cure more difficult. In order for metastasis to occur, cancer cells must gain motile and invasive phenotypes. As one of the keystone proteins involved in cell motility and invasion, Focal Adhesion Kinase (FAK) has emerged as a good therapeutic target for the inhibition of metastases via targeted drug design and small molecule inhibitors. Accordingly, a small molecule inhibitor has recently been developed against FAK activation and signaling. However, drug resistance is common among targeted therapies. Development and classification of drug resistant cells elucidated the possible mechanism behind FAK inhibitor resistance such that second-line therapy drugs can be designed to overcome or avoid resistance. The overall data presented herein support the role of FAK as an important drug target in cancer metastasis as well as provide insight and direction for future FAK inhibitor design.<br>Dans la progression du cancer, le développement de métastases est caractéristique de la phase terminale et rend le traitement difficile. Afin que des métastases se dévelopment, les cellules cancéreuses doivent acquérir de la motilité ainsi qu'un phénotype invasif. Considéré come l'une des plus importantes protéines participant dans la motilité cellulaire, la prot éine Focal Adhesion Kinase (FAK) a émergé comme une bonne cible thérapeutique pour l'inhibition de métastases par la création de drogues ciblées et de petites molécules inhibitrices. Par conséquent, une molécule inhibitrice de l'activation de FAK et sa signalisation a été récemment développée. Cependant, J'ai demontré que la résistance est commune parmis ces drogues. Le dévelopement et la classification des clones de cellules résistantes ont permi d'élucider un mécanisme impiquant en partie une amplification de l'activité FAK; ce mécanisme permetter a de découvrir des analogues de deuxième génération pour surmonter ou éviter la résistance. L'ensemble de données présentées ci-dessous supportet le rôle de FAK comme une cible importante dans la prévention de métastases et exposent les futur directions pour contourner la résistance aux inhibiteurs de FAK.
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Harrison, O. J. "The molecular mechanism of cadherin-mediated adhesion." Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603783.
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My work examines the role of a conserved tryptophan residue, Trp2, in the adhesive domain of cadherins that has been shown to be essential for their adhesive function. Structural studies have shown Trp2 to be integrated into its own cadherin domain, integrated into the domain an opposing cadherin molecule, or freed from the domain and exposed to solvent. Until now, the physiological relevance of these structures has been controversial. Using conformation specific antibodies I show that Trp2 integrates into the domain fold of its own cadherin molecule in physiological conditions, but that this integration is not stable owing to structural constraints imposed by calcium binding to the cadherin. This raises the possibility that Trp2 could participate in intermolecular interactions during adhesion by inserting into opposing cadherins in what is referred to as the strand exchange model of cadherin adhesion. This model is tested directly by introducing cysteine substitutions into opposing cadherins such that disulphide bonds can form between them during adhesion only if they engage in strand exchange. The results provide clear evidence that strand exchange is central to adhesion by classical cadherins. Further results demonstrate that exchange of Trp2 in this way is stabilised by formation of a salt bridge. By disrupting this salt bridge with point mutations we find that if the tendency of Trp2 to integrate into its own domain and thus be unavailable for adhesion is inhibited, adhesion can be greatly enhanced. Our results thus define the mechanism of cadherin adhesion as a dynamic balance between the conflicting tendencies of Trp2 to engage in intramolecular and intermolecular interactions.
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Minett, William T. "Cell adhesion on synthetic polymer substrates." Thesis, Aston University, 1986. http://publications.aston.ac.uk/14512/.
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Cho, Jae Youl. "Molecular mechanism of CD98 function." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249677.
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Wu, Tao. "Structure-function analysis of vascular tethering molecules using atomic force microscope." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/31844.
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Thesis (Ph.D)--Mechanical Engineering, Georgia Institute of Technology, 2009.<br>Committee Chair: Zhu, Cheng; Committee Member: Barry, Bridgette; Committee Member: Boyan, Barbara; Committee Member: McEver, Rodger; Committee Member: McIntire, Larry. Part of the SMARTech Electronic Thesis and Dissertation Collection.
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Eriksson, Malin. "The Influence of Molecular Adhesion on Paper Strength." Doctoral thesis, Stockholm, Department of Fibre and Polymer Technology, School of Chemical Science and Engineering, KTH, Royal Institute of Technlology, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4101.
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Buehler, Betul. "Molecular Adhesion and Friction at Elastomer/Polymer Interfaces." University of Akron / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=akron1164649632.
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Killock, David James. "Molecular characterisation of L-selectin-dependent adhesion and signalling." Thesis, Imperial College London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.512055.
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Gideonsson, Pär. "Helicobacter pylori : molecular insights into regulation of adhesion properties." Doctoral thesis, Umeå universitet, Institutionen för medicinsk kemi och biofysik, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-120466.
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Helicobacter pylori infects the human stomach and triggers an inflammatory response that damages the gastric tissue. This host-pathogen interplay has dire consequences as up to 20 % of infected individuals develop peptic ulcer disease or gastric cancer. Given that half of the world’s population is infected, the number of afflicted humans is staggering and also tells that H. pylori is extremely efficient in spreading and maintaining infection. To enable persistent infection many factors play a role, but one important feature of H. pylori is its impressive ability to adhere to the slimy gastric mucus layer and the underlying epithelial cells. This occurs mainly via the BabA and SabA proteins that bind ABO/Leb- and sLex/sLea-antigens. I have in my thesis studied how these two proteins are utilized and regulated. H. pylori transcription is in part controlled by two-component systems (TCSs) that use a sensor protein and a DNA-binding response regulator. We have studied how these systems control sabA and to some extent babA and indeed found a better map of how sabA and babA is regulated at the transcriptional level. We also found that variations in a polynucleotide T-tract located in the sabA promotor could fine-tune SabA expression/ sLex-binding. Thus we have exposed how strict regulation by TCSs combined with stochastic processes together shapes attachment in the bacterial population. As the buffering mucus layer is constantly exfoliated, placing H. pylori in bactericidal acid, we hypothesized that low pH should abrogate adhesion. SabA expression was indeed repressed in low pH, however BabA expression remained unaffected. The BabA/ Leb-binding was instead directly reversibly hampered by low pH and the degree of pH sensitivity was strain dependent and encoded in the BabA sequence. We believe that the pH dependent loss of binding is one key factor H. pylori utilizes to maintain persistent infection. BabA is divided in generalists that bind ABO antigens and specialists that only bind blood group (bg) O. We co-crystalized BabA bound to these receptors and established the structural basis for generalist vs. specialist discrimination. We furthermore found a disulfide-clasped loop (CL2) in the center of the binding domain crucial for binding. Breaking CL2 with N-Acetylcysteine (NAC) disrupted binding and H. pylori infection mice experiments revealed inflammatory reduction upon NAC-treatment. In sum, I have in my thesis dissected how H. pylori controls its adhesive abilities and how intrinsic properties in binding can be exploited for therapeutic purposes.
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Piper, James Wilson. "Force dependence of cell bound E-selectin/carbohydrate ligand binding characteristics." Diss., Georgia Institute of Technology, 1997. http://hdl.handle.net/1853/18388.
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Sjöström, Annika E. "Pathogenecity-associated genes modulate Escherichia coli adhesion and motility." Doctoral thesis, Umeå universitet, Molekylärbiologi (Medicinska fakulteten), 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-22302.
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Escherichia coli strains typical of UPEC (uropathogenic E. coli) and NBM (newborn meningitis) isolates carry chromosomally located PAIs (pathogenicity islands) that are absent in non-pathogenic E. coli strains. The PAIs include genes for virulence factors such as toxins and genes coding for specific adhesins and pili/fimbriae formation. Commonly, the gene clusters for such fimbriae in E. coli consist of a set of genes for biogenesis of the actual fimbriae organelles: a chaperone, an usher, the fimbrial subunits, and an adhesin, as well as some regulatory genes. Genetic studies of the fimbrial gene clusters in PAIs containing the pap genes, the prs genes, or the sfa genes led to the discovery of nearby open reading frames coding for putative cytoplasmic 17 kDa proteins — the X genes. Molecular genetic studies of the sfaXII locus in the clinical NMEC isolate IHE3034 have been performed. The results suggested that expression of the sfaXII gene had regulatory functions affecting both type 1 fimbriae expression and the flagella-mediated motility. Type 1 fimbriae expression was found to be affected at the level of fim operon transcription and a major reason was SfaXII-mediated modulation of expression from the fimB and fimE recombinase genes. Quantification of SfaII-fimbriated bacteria in a comparison between wild type and SfaXII mutant strains gave no indication that the sfaXII gene product also would be affecting expression and/or biogenesis of SfaII fimbriae. Biomechanical properties of the SfaII fimbriae produced by wild type and the sfaXII mutant IHE3034 were studied using force measuring optical tweezers (FMOT) and compared to other PAI-encoded fimbriae as well as to the type 1 fimbriae encoded on the core chromosome. The FMOT methodology assesses unfolding and refolding properties and we found that S fimbriae had weaker layer-to-layer interactions than both P and type 1 fimbriae, however the unfolding kinetics was slightly faster. The expression profile and regulation of the sfaXII gene were determined by use of reporter gene fusions and it was found that expression was affected by environmental cues such as pH, osmolarity and temperature. It was also discovered that the nucleoid structuring protein H-NS and the sigma factor RpoS had strong direct or indirect repressive effects on sfaXII gene expression. Further genomic analysis of the PAI fimbrial operons revealed that in some cases an additional ORF was found between the X genes and the fimbrial adhesion genes. Examination of the sfaII operon in IHE3034 indicated that this new gene, denoted sfaYII, coded for a protein that had the EAL domain motif and thereby could be considered a putative phosphodiesterase involved in controlling the level of cyclic-di-GMP in the bacterial cells.
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Afar, Daniel E. H. "Phosphorylation and cell adhesion properties of myelin-associated glycoprotein isoforms." Thesis, University of Ottawa (Canada), 1992. http://hdl.handle.net/10393/7517.
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The phosphorylation and cell adhesion properties of myelin-associated glycoprotein (MAG) isoforms were investigated. MAG is a member of the immunoglobulin supergene family and is thought to mediate interactions between myelinating glial cells and neurons in the central and peripheral nervous systems. Two isoforms of MAG exist, L-MAG and S-MAG, which exhibit differential expression patterns. Using retroviral infection and transfection of the cDNAs encoding L-MAG and S-MAG, L cell fibroblasts and NIH3T3 cell lines that express either isoform were generated. The expression of both isoforms on the cell surface of L cells induced the cells to aggregate in a MAG-dependent fashion. The adhesion phenomenon was determined to be calcium and temperature independent. A critical level of cell surface MAG expression was required for cell aggregation to occur. The adhesion was found to be heterotypic in nature, signifying the presence of a MAG receptor on the cell surface of L cells. The MAG isoforms are identical in their extracellular and transmembrane domains. They share a common region in their cytoplasmic domain, but are distinct at their carboxyl termini. The unique carboxyl tails are comprised of 54 amino acids in L-MAG and 10 residues in S-MAG. Both isoforms were determined to be phosphorylated in fibroblasts. L-MAG exhibited phosphorylation on serine, threonine and tyrosine residues. The phosphorylation on tyrosine was augmented by treatment of cells with ammonium vanadate. S-MAG phosphorylation occurred mainly on serine residues, but some phosphotyrosine was also detected. The phosphorylation of S-MAG, however, was relatively insensitive to vanadate treatment. Tryptic digest analysis showed that two serine and the major tyrosine phosphorylation site in MAG were identical in L-MAG and S-MAG. The major tyrosine phosphorylation site in MAG was, thus, identified as tyrosine 558. This tyrosine residue is homologous to the major tyrosine phosphorylation site in the fibronectin receptor, integrin. A similar phosphorylation pattern of L-MAG was observed in primary rat oligodendrocytes. Determination of the stoichiometry of phosphorylation revealed that phosphorylation of L-MAG was at least one order of magnitude greater than S-MAG, especially with respect to tyrosine phosphorylation. This result indicates the presence of a carboxyl terminal sequence unique to L-MAG that activates the phosphorylation of tyrosine 558. This region may represent docking sites for protein tyrosine kinase binding, making L-MAG-kinase interactions more efficient. Two populations of L-MAG molecules were discovered: those that are phosphorylated on tyrosine residues, and those that exhibit serine/threonine phosphorylation. In effect, tyrosine phosphorylation precludes serine/threonine phosphorylation, suggesting that the alternatively phosphorylated L-MAG molecules perform different functions. Increasing the tyrosine phosphorylation of MAG had no detectable effect on the cell adhesion behaviour of the cells. Tyrosine phosphorylation of L-MAG, however, induced its capacity to bind the SH2 domain of phospholipase C-gamma. Therefore, L-MAG has the potential to interact with a variety of signalling molecules via its cytoplasmic domain. While L-MAG may participate in signal transduction pathways, S-MAG may function in a more restricted manner and perform only as a cell adhesion molecule. Thus, the differential regulation of MAG isoform expression may serve to increase the repertoire of MAG functions at specific times during development.
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Leung, Yu Hing Nelly. "Carcinoembryonic antigen cell adhesion molecule 1: cancer and metabolic regulation." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=18740.
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Carcinoembryonic antigen cell adhesion molecule 1, CEACAM1, is a glycoprotein and a member of the CEA (carcinoembryonic antigen) family of genes. It is expressed on the surface of epithelial, endothelial, and hematopoietic cells, within the gastrointestinal tract, reproductive organs, liver, lungs and kidney. CEACAM1 plays a role in inhibiting the immune response, in cell adhesion, in insulin clearance, in cellular apoptosis and proliferation, in angiogenesis, and functions as a tumor suppressor. In humans, CEACAM1 is dysregulated and often lower in hyperplastic lesions than in normal tissue, especially in cases of colon, prostate, liver, and 30% of breast cancers. The role of CEACAM1 in tumor formation was studied using the Ceacam1-/- mouse model, which sustained systemic ablation of CEACAM1. In the absence of CEACAM1, epithelial cells from small intestine and colon undergo less apoptosis than in wild-type cells. Moreover, there is increased proliferation in the Ceacam1-/- colonocytes. As CEACAM1 inactivation alone is not sufficient to induce tumors in the mice, the chemical carcinogen, azoxymethane, was used to induce colon tumors. Ceacam1-/- mice developed a higher tumor burden than wild-type mice. One drawback to chemical carcinogenesis is that multiple mutations in unidentified genes cause tumors. To understand the contribution of CEACAM1 to tumor development, the Ceacam1-/- mice was mated with the genetically modified mouse Apc1638N/+ that spontaneously forms small intestinal tumors. Compound Apc1638N/+: Ceacam1-/- mice developed more tumors than Apc1638N/+ mice, and these tumors progressed to a more advanced stage. In addition, Ceacam1-/- enterocytes showed compromised Wnt signalling. The Ceacam1-/- mouse is also a model for obesity and CEACAM1 is a key factor in insulin clearance. Due to defective insulin clearance, the Ceacam1-/- mice suffer from insulin resistance, and altered lipid synthesis. As these mice age, their weight and abdominal<br>La glycoprotéine CEACAM1 (Carcinoembryonic antigen cell adhesion molecule 1) est une molécule d'adhésion appartenant à la famille des CEA (Antigène carcinoembryonnaire). CEACAM1 se retrouve à la surface des cellules épithéliales, endothéliales, et hématopoétiques, du tube digestif, des organes reproducteurs, du foie, des poumons et des reins. CEACAM1 présente plusieurs fonctions: inhibition de la réponse immunitaire, adhésion cellulaire, clairance de l'insuline, apoptose et prolifération cellulaire, angiogénèse, et rôle de suppresseur de tumeurs. L'expression de CEACAM1 est souvent diminuée dans plusieurs cas de cancers humains dont le côlon, le foie, la prostate, et 30% des cancers du sein. Le modèle de souris Ceacam1-/- a été utilisé afin d'étudier le rôle de CEACAM1 dans la formation de tumeur. En l'absence de CEACAM1, le tissu épithélial de l'intestin grêle et du côlon subit moins d'apoptose. En contrepartie, une augmentation de la prolifération est détectée dans le côlon des souris Ceacam1-/-. L'absence de CEACAM1 n'étant pas suffisante pour induire l'apparition de tumeurs, nous avons utilisé un cancérogène chimique, l'azoxymethane. Les tumeurs observées dans le côlon des souris Ceacam1-/- s'avèrent être plus importantes que celles des souris contrôles. Le désavantage de l'utilisation de l'azoxymethane est que celui-ci provoque des mutations dans plusieurs gènes plus ou moins définis. Afin de comprendre la contribution de CEACAM1 dans le développement tumoral, la souris Ceacam1-/- a été croisée avec la souris Apc1638N/+ qui forme spontanément des tumeurs dans l'intestin grêle. Les souris Apc1638N/+: Ceacam1-/- développent plus de tumeurs présentant un phénotype tumoral plus agressif que celui formé dans les souris Apc1638N/+. Par ailleurs, les cellules épithéliales de l'intestin grêle Ceacam1-/- montrent une dérégulation de la voie de signalisation Wnt. CEACAM1 étant un facteu
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Gandhi, Neha Sureshchandra. "Molecular modelling of platelet endothelial cell adhesion molecule 1 and its interaction with glycosaminoglycans." Thesis, Curtin University, 2007. http://hdl.handle.net/20.500.11937/1513.
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The Platelet Endothelial Cell Adhesion Molecule 1 (PECAM-1) has many functions including its roles in leukocyte extravasation as part of the inflammatory response, and in the maintenance of vascular integrity through its contribution to endothelial cell-cell adhesion. Various heterophilic ligands of PECAM-1 have been proposed. The possible interaction of PECAM-1 with glycosaminoglycans (GAGs) is the focus of this thesis. The three dimensional structure of the extracellular immunoglobulin (Ig)-domains of PECAM-1 was constructed using homology modelling and threading methods. Potential heparin/heparan sulfate binding sites were predicted on the basis of their amino acid consensus sequences and a comparison with known structures of sulfate binding proteins. Heparin and other GAG fragments have been docked to investigate the structural determinants of their protein binding specificity and selectivity. It is predicted that two regions in PECAM-1 appear to bind heparin oligosaccharides. A high affinity binding region was located in Ig-domains 2 and 3 and a low affinity region was located in Ig-domains 5 and 6.These GAG binding regions are distinct from regions involved in PECAM-1 homophilic interactions. Docking of heparin fragments of different size revealed that fragments as small as a pentasaccharide appear to be able to bind to domains 2 and 3 with high affinity. Binding of longer heparin fragments suggests that key interactions can occur between six sulfates in a hexasaccharide with no further increase in binding affinity for longer fragments. Molecular dynamics simulations were also used to characterise and quantify the interactions of heparin fragments with PECAM-1. These simulations confirmed the existence of regions of high and low affinity for GAG binding and revealed that both electrostatic and van der Waals interactions determine the specificity and binding affinity of GAG fragments to PECAM-1. The simulations also suggested the existence of ‘open’ and ‘closed’ conformations of PECAM-1 around domains 2 and 3.
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McNulty, Clare A. "Studies on the molecular basis of eosinophil adhesion to endothelium." Thesis, University of Leicester, 2001. http://hdl.handle.net/2381/29391.
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Selective adhesion may be important for the preferential accumulation of eosinophils in asthma and allergic diseases. The Stamper-Woodruff frozen section assay (FSA) was used to define the adhesion of human peripheral blood eosinophils and neutrophils to endothelium in a model of chronic airway inflammation, the nasal polyp. Eosinophil and neutrophil adhesion to nasal polyp endothelium (NPE) was (32 integrin-dependent. Eosinophil adhesion was inhibited to a lesser extent by mAbs against pi integrins and VCAM-1. Adhesion of both eosinophils and neutrophils to NPE was activation-dependent. as shown by inhibition with azide. Neutrophil adhesion was mediated by PAF and IL-8 signalling through pertussis toxin (PTX)-scnsitive G-protein coupled receptors (GPCR). In contrast, eosinophil adhesion was PTX-insensitive. and the chemokine receptor CCR3 was not involved. The eosinophil activation step was further explored under shear flow conditions. Neutrophils firmly arrested on TNF-a-stimulated human umbilical vein endothelial cells (HUVEC) under flow. In contrast, eosinophils rolled unless exogenous chemoattractants such as PAF, eotaxin, and RANTES were added. Priming eosinophils with IL-5 before addition to HUVEC caused arrest of the entire population. The flow assay was also used to investigate the receptors involved in leukocyte adhesion to IL-13- stimulated HUVEC. Eosinophils but not neutrophils showed enhanced binding to IL-13- stimulated HUVEC compared to medium-cultured cells. This adhesion was mediated by P-selectin/ PSGL-1. and to a lesser extent VLA-4/ VCAM-1. These findings were consistent with the pattern of adhesion receptor expression in nasal mucosa, with weak expression of VCAM-1 compared with P-selectin. In summary, I have demonstrated a difference in integrin usage and the mechanism of integrin activation between eosinophils and neutrophils. An additional priming step in the adhesion cascade appears to be required for eosinophils, but not neutrophils, to respond to an activating stimulus and arrest on endothelium. P-selectin/ PSGL-1 interactions were pivotal to eosinophil arrest on Th2- cytokine-stimulated endothelium and are potential targets for inhibition of eosinophil migration.
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Wright, Ann Heather. "The molecular basis of leukocyte adhesion deficiency in six patients." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239257.
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Cooper, Sharon Rose. "δ-Protocadherin Function: From Molecular Adhesion Properties to Brain Circuitry". The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1492457066344753.
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Chen, Wei. "Molecular dynamics simulations of binding, unfolding, and global conformational changes of signaling and adhesion molecules." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/28118.
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Thesis (M. S.)--Mechanical Engineering, Georgia Institute of Technology, 2009.<br>Committee Chair: Zhu, Cheng; Committee Member: Harvey, Stephen; Committee Member: Hud, Nicholas; Committee Member: Zamir, Evan; Committee Member: Zhu, Ting.
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Källström, Helena. "Molecular and cellular mechanisms during adherence and cell signaling of pathogenic Neisseria to host cells /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3848-2/.
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Zhou, Hua 1963. "Molecular mechanisms of intercellular adhesion mediated by carcinoembryonic antigen family members." Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41172.
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Carcinoembryonic antigen (CEA), an immunoglobulin (Ig) superfamily member, functions as an adhesion molecule in vitro. This thesis reports that nonspecific cross-reacting antigen (NCA), a CEA family member, can mediate Ca$ sp{++}$-independent, homotypic intercellular adhesion in vitro. Heterotypic adhesion studies demonstrate that CEA can cross-interact with NCA; however, neither NCA nor CEA can interact with other Ig superfamily members such as neural cell adhesion molecule (NCAM) and myelin-associated glycoprotein. This specificity was used to investigate the mechanism of CEA-CEA binding using CEA truncated and CEA/NCAM chimeric constructs. A novel model has been proposed in which double reciprocal interactions between the V-like domains and C-like domains of antiparallel CEA molecules result in strong binding between CEA on apposing cell surfaces. Furthermore, the specificity of a library of anti-CEA monoclonal antibodies was defined; their effects on CEA-mediated adhesion further support the CEA-binding model.
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Nicholson, Martin William Michael. "Molecular analysis of the leukocyte cell-surface adhesion protein L-selectin." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260752.
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Shirure, Venktesh S. "Molecular Mechanisms of Circulating Tumor Cell Adhesion in Breast Cancer Metastasis." Ohio University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1357706517.
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Perera, Hettiarachchige Dhanuja Deepamalee. "Molecular Basis of the Role of Kindlin 2 in Cell Adhesion." Cleveland State University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=csu1295461683.
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Carulli, Sonia. "Molecular basis of syndecan-1 mediated cell adhesion to laminin 332." Thesis, Lyon 1, 2011. http://www.theses.fr/2011LYO10134.
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L’interaction du récepteur syndecan-1 de la famille des héparanes sulfates protéoglycanes avec le fragment carboxy-terminal alpha3LG4/5 de la protéine d’adhérence matricielle, la laminine 332, induit une réorganisation du cytosquelette de la cellule conduisant à la formation de filopodes et de microspicules, caractéristiques de la migration cellulaire. Notre laboratoire a mis en évidence que l’adhésion cellulaire syndecan-1 dépendante implique les chaînes d’héparanes sulfates et chondroïtine sulfate. Afin d’identifier le (les) zone(s) impliquée(s) dans l’interaction domaine LG4/5-syndécan-1, une approche de mutagenèse dirigée a été mise en place sur le fragment LG4/5 recombinant. Les résidus conservés parmi les laminines, identifiés dans la littérature comme liant l’héparine, aussi bien que des résidus basiques spécifiques à la chaine α3 identifiés par des approches prédictives, ont été remplacés par le résidu neutre glutamine. Toutes les protéines couplées avec l’étiquette 6-Histidine ont été produites dans des cellules de mammifère, purifiées par chromatographie d'affinité et caractérisées biochimiquement et par dichroïsme circulaire. L’évaluation de l’affinité des protéines produites pour l’héparine nous a permis d’identifier un site d’interaction majeur avec les glycosaminoglycanes dans le domaine LG4/5, entouré par des résidus à mineur affinité. La technique de résonance plasmonique de surface et des tests d’adhérence cellulaire nous ont permis de confirmer ce résultat puisque l’absence du site d’interaction majeur avec l’héparine a produit une inhibition totale de l’adhérence. Des expériences de pull-down nous ont montré que ce site est aussi impliqué dans l’interaction avec le syndecan-4, indiquant que cette séquence pourrait ainsi jouer un rôle dans différents processus cellulaires. Une collaboration avec des bio-informaticiens nous a permis de proposer un modèle structural du domaine LG4/5 et de montrer que la zone identifiée est localisée dans une boucle exposée à l’extérieure du module LG4, entourée par des résidus à plus faible affinité<br>The HSPG receptor syndecan-1 interacts with the carboxy-terminal LG4/5 domain in laminin 332 to participate in keratinocyte migration by inducing formation of cytoskeleton related protrusive structures. We have shown that syndecan-1 mediated cell adhesion occurs in heparan sulphate and chondroitin sulphate dependent manner and that these two glycosaminoglycan (GAG) chains bind independently to LG4/5 with different affinities. To identify residues involved in the interaction of the LG4/5 domain with syndecan-1 and to apprehend the molecular basis of the GAGs interaction specificity, we have used a site-directed mutagenesis approach of the recombinant LG4/5 fragment. The residues identified as conserved heparin binding residues throughout laminins, as well as “candidate” basic residues identified through predictive approaches, have been replaced by the neutral residue glutamine. All LG4/5 proteins carrying a hexa-histidine tag at their C-terminal end were expressed in mammalian cells. The produced proteins were purified and characterized biochemically. Circular dichroism studies performed on all mutagenised proteins showed that the overall structure of each mutant is comparable to that of the wild type protein. Heparin affinity chromatography analysis allowed us to identify a major heparin binding site in the LG4/5 domain surrounded by several minor GAG binding sites. Surface plasmon resonance analysis of mutated LG4/5 proteins-heparan sulphate interaction confirmed these results. These findings were well correlated with our in cellulo syndecan-1 mediated cell adhesion as the lack of this major heparin binding site totally abrogated cell adhesion. Pull down experiments allowed us to show that this heparin binding site sequence is responsible not only for the interaction of the receptors syndecan-1 but also for syndecan-4 suggesting that additional cellular functions may be carried by this sequence. Our structural predictions suggest that the LG4/5 in laminin 332 encompasses a major GAG binding site surrounded by a track of converging positively charged residues
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Hur, Sunyoung. "Molecular mechanism of barnacle adhesion : a structural approach and underlying biochemistry." Electronic Thesis or Diss., Sorbonne université, 2022. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2022SORUS572.pdf.
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Les balanes adhèrent de manière robuste et permanente à divers substrats sous-marins grâce à de fortes interactions d’une couche complexe multiprotéique appelée « ciment ». Cependant, les interactions intermoléculaires responsables des fortes propriétés adhésives du ciment de bernacle restent mal comprises. Une hypothèse centrale de cette thèse est que les propriétés sous-marines du complexe cimentier sont intimement liées aux caractéristiques moléculaires des protéines de ciment (CP) formant le complexe de ciment. Des études antérieures ont montré que le ciment est fait de nanofibrilles de type amyloïde qui peuvent contribuer à l’adhérence. Cependant, la protéine responsable de la formation de ces nanofibrilles reste inconnue. Dans cette étude, les caractéristiques morphologiques à l’échelle nanométrique des protéines de ciment recombinantes (CP) de la balane Megabalanus rosa (MrCP19 et MrCP20, avec les chiffres indiquant un poids moléculaire de 19 kDa et 20 kDa respectivement) ont été caractérisées par la mesure du dichroïsme circulaire (CD), le test Thioflavin T (ThT), la microscopie à force atomique (AFM) et la microscopie électronique à transmission (TEM), suggérant le potentiel de former des structures nano-fibrillaires dans certaines conditions. Sur la base de la structure primaire et de la morphologie de surface des protéines, des études mécaniques, biochimiques et antimicrobiennes ont été menées pour comprendre les rôles uniques de ces protéines interfaciales sur la croissance des balanes et le processus d’attachement à la surface, par exemple la biominéralisation et le contrôle de la biodégradation. Les mesures effectuées à l’aide de l’appareil de force de surface (SFA) et de la microbalance à cristaux de quartz avec surveillance de la dissipation (QCM-D) ont montré que les interactions électrostatiques jouent un rôle clé dans l’adsorption et l’adhésion de surface de MrCP19 et MrCP20. En outre, l’influence mutuelle de la croissance de la plaque de base de bernacle (minéralisation de carbonate de calcium) et de la fibrillation de la protéine de ciment MrCP20 adjacente a été étudiée à l’aide de surfaces d’or fonctionnalisées monocouches (SAM) auto-assemblées, de spectroscopie Raman, de QCM-D, de spectromètre photoélectronique à rayons X (XPS) et de spectroscopie infrarouge à transformée de Fourier à réflectance totale atténuée (ATR-FTIR). Parallèlement, l’influence du substrat externe adjacent à la protéine de ciment MrCP19 sur les cellules bactériennes présentes dans le biofilm sur les surfaces sous-marines en milieu marin a été démontrée à l’aide de différents tests microbiologiques, notamment le test de zone d’inhibition, le test de concentration minimale inhibitrice (CMI), la MET, l’étude de fluorescence, etc. Plus intéressant encore, une hypothèse intrigante concernant le processus de fibrillation amyloïde et l’activité antimicrobienne a été suggérée. Sur la base de ces examens préliminaires, les deux PC interfaciaux ont montré des responsabilités potentielles distinctes sur le tassement des bernacles, non seulement avec son adhérence, mais aussi avec d’autres rôles fonctionnels aux interfaces. Ces travaux amélioreront nos connaissances sur les contributions individuelles de MrCP19 et MrCP20 dans le complexe cimentier et donc dans la capacité globale d’adhésion sous-marine des balanes. À cet égard, la thèse vise à fournir des lignes directrices moléculaires pour le développement de mimiques polymères inspirés des PC (à base de peptides ou de protéines) à partir de ce système moléculaire bio-adhésif<br>Barnacles adhere themselves robustly and permanently to diverse underwater substrates through strong interactions of a multi-protein complex layer called the “cement”. However, the intermolecular interactions responsible for the strong adhesive properties of the barnacle cement remains poorly understood. A central hypothesis of this thesis is that underwater properties of the cement complex are intimately linked to the molecular characteristics of cement proteins (CPs) forming the cement complex. Previous studies have shown that the cement is made of amyloid-like nanofibrils that may contribute to adhesion. However, the protein responsible for the formation of these nanofibrils remain unknown. In this study, the nanoscale morphological features of recombinant cement proteins (CPs) from the barnacle Megabalanus rosa (MrCP19 and MrCP20, with the numbers indicating molecular weight of 19 kDa and 20 kDa respectively) were characterized by Circular Dichroism (CD) measurement, Thioflavin T (ThT) assay, Atomic Force Microscopy (AFM), and Transmission Electron Microscopy (TEM), suggesting the potential to form nano-fibrillar structures under certain conditions. Based on the proteins’ primary structure and surface morphology, mechanical, biochemical, and antimicrobial studies were conducted to understand the unique roles of these interfacial proteins on barnacle growth and surface attachment process, for instance biomineralization and biodegradation control. Measurements using Surface Force Apparatus (SFA) and Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) illustrated that electrostatic interactions play a key role in surface adsorption and adhesion of MrCP19 and MrCP20. In addition, the mutual influence of barnacle base plate growth (calcium carbonate mineralization) and the adjacent cement protein MrCP20 fibrillation was investigated using self-assembled monolayer (SAM) functionalized gold surfaces, Raman spectroscopy, QCM-D, X-ray photoelectron spectrometer (XPS), and Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). Concurrently, the influence of the external substrate adjacent cement protein MrCP19 on bacteria cells which are present in biofilm on underwater surfaces in marine environment was demonstrated using different microbiology tests including zone of inhibition test, Minimum inhibitory concentration (MIC) assay, TEM, fluorescence study, and so on. More interestingly, an intriguing hypothesis regarding amyloid fibrillation process and antimicrobial activity was suggested. Based on these preliminary examinations, the two interfacial CPs showed distinctive potential responsibilities on barnacle settlement not only with its adhesion but also with other functional roles at the interfaces. This work will improve our knowledge about individual contributions of MrCP19 and MrCP20 in cement complex and hence in overall underwater adhesion capacity of barnacles. In this regard, the thesis aims at providing molecular guidelines towards the development of CPs inspired polymeric (peptide or protein based) mimics from this bio-adhesive molecular system
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Loumrhari, Fatine. "Investigation of Rab GTPase interaction with focal adhesion proteins in breast cancer cells." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86771.
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The acquisition of cancer cell invasive properties is a critical early event in primary cancer progression to metastasis. Increasing experimental and clinical evidence supports that metastasis formation is initiated by the acquisition of cancer cell motile properties driven by extensive remodelling of the cell cytoskeleton and dynamic recycling of focal adhesion proteins (FA); the later link the extracellular matrix to the cell cytoskeleton and intracellular signaling. Cancer cell invasion has been associated with elevated expression/activation of several proteins, including members of Rab GTPases. These proteins are key regulators of membrane trafficking of proteins and membrane receptor recycling, including that of integrins. Elevated expression of Rab GTPases has been linked to increased cell migration and invasion. Previously, biochemical and proteomic studies from my host laboratory, using paired non-invasive and invasive breast cancer cells have revealed a rapid turnover of FA proteins in invasive compared to non-invasive cancer cells, as well as differential expression of several Rab GTPase members, including Rab5, Rab11 and Rab7. Thus, I tested the hypothesis that Rab GTPases may regulate FA protein turnover, in part via interaction with focal adhesion kinase (FAK), a central protein of master focal adhesion signalling. Immunofluorescence and immunoprecipitation assays reveal that Rab11 and FAK interact and colocalize at FA sites. Development of cell lines where Rabs are depleted using siRNA revealed an impact of Rab on cell migration; Rab inhibition inhibited cell migration. I propose that Rab GTPases, and in particular Rab11 may contribute to the regulation of FAK function in FA turnover and cell migration.<br>Le cancer invasif du sein reste une maladie extrêmement courante et une cause majeure de mortalité parmi les personnes atteintes du cancer. Un événement par lequel les cellules du cancer se propagent est initié par l'acquisition de propriétés mobiles conduites par le remodellement du cytosquelette cellulaire et par le roulement dynamique de protéines d'adhérence focale (FA); relient la matrice extracellulaire au cytosquelette cellulaire. Le cancer invasif du sein a été associé avec l'expression élevée de certaines proteines surnommées les Rab GTPases. Ils sont connus comme des regulateurs essentiels dans la circulation membraneuse y compris le recyclage des recepteurs incluant celles des integrins, protéines d'adhérence focale qui agissent en tant que mediateur pour l'adherence des cellules a la matrice extracellulaire. Leur expression élevée, a en fait, favorisé la migration et l'invasion des cellules, contribuable a la métastase du cancer. Auparavant, des études "proteomiques" sur des cellules non-invasives contre des cellules invasives du cancer du sein ont révélé un roulement rapide de protéines d'adhérence focales (FA) dans les cellules invasives, ainsi q'une expression différentielle de plusieurs membres de Rab GTPases, y compris Rab5, Rab11 et Rab7. Ainsi, nous testons l'hypothèse que Rab GTPase interagit avec la protein kinase d'adhérence focale (FAK), qui sert comme mediateur pour les voies de transduction des signaux aux sites d'adherence focale. Nous supposons aussi que les Rabs pourraient jouer un role important dans la regulations de la circulation de FA dans le cancer invasive du sein. Les experiences faites avec l'immunofluorecence et l'immunoprecipitation révèlent que Rab11 et FAK interagissent et colocalisent ensembles. Le développement de lignes de cellules où les Rabs ont été diminués en utilisent le siRNA démontre son effet sur la migration de cellules. Je propose que Rab11 est un élément decisif qui po
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McCuaig, Kimberly. "Alternative splicing and adhesion properties of a mouse carcinoembryonic antigen gene family member." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=56679.
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Carcinoembryonic antigen (CEA) is a tumor marker used clinically to assess post-operative recurrences of breast, lung and colon cancers. The CEA gene family, which is part of the immunoglobulin superfamily, is composed of several proteins crossreactive with anti-CEA antibodies. Carcinoembryonic antigen appears to function in the development of the gastro-intestinal tract as well in tumor formation; it is capable of mediating cell-cell adhesion in vitro which is consistent with its putative role of maintaining tissue architecture in vivo. CEA gene family members have also been identified in various tissues of the mouse. Two of the mouse proteins, mmCGMla and mmCGMlb, have been characterized. By sequence homology, mmCGMla and mmCGMlb are the mouse homologues of human biliary glycoprotein and of rat hepatocyte ecto-ATPase. Both of the mouse CEA related proteins function as adhesion molecules when expressed on the cell surface of transfectant cells; however, mmCGMla, unlike mmCGMlb, mediates cellular aggregation irrespective of calcium concentration or temperature. Sequence comparison of mmCGMla, mmCGMlb, and other cDNAs isolated by polymerase chain reaction techniques, demonstrates that there are at least eight possible transcripts encoding CEA-related proteins and that these transcripts are all produced by alternative splicing of one precursor messenger RNA.
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Efstathiou, Jason Alexander. "The role of adhesion molecules in colorectal carcinogenesis." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670210.
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Gann, Reed N. "Host Signaling Response to Adhesion of Bifidobacterium infantis." DigitalCommons@USU, 2010. https://digitalcommons.usu.edu/etd/586.
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Investigations of the molecular binding partners of the probiotic bacterium Bifidobacterium longum subspecies infantis (B. infantis) and the pathogen Salmonella enterica subspecies enterica serovar Typhimurium LT2 (Salmonella ser. Typhimurium) found that these two very different bacteria bind gangliosides. However, these organisms lead to completely different host health outcomes when present in the gut. B. infantis is the founding microbial population in the intestinal tract of breast-fed infants. S. typhimurium is the most important food-borne pathogen that results in humans. This study used an in vitro gut epithelial cell model to examine the host cellular response to adhesion of B. infantis, which led to an increase in intestinal epithelium survival. This observation led to a series of experiments to elucidate the pathway for host signaling initiated by adherence of B. infantis to the host membrane to explain the increase in host cell survival. B. infantis adhesion induced significant (q≤0.05) differential expression of 208 host genes. These genes were associated with increased broad mechanisms of cell survival that included BIRC3, TNFAIP3, and SERPINB9. We hypothesized that a biochemical link existed between the host membrane adhesion protein and the increase in cell survival, mediated via AKT. We tested this hypothesis to demonstrate that B. infantis interaction initiated signal transduction using G-proteins via phosphorylation of AKT and induced production of the BIRC3, TNFAIP3, and SERPINB9. This study discovered adhesion of B. infantis initiated activation of AKT via phosphorylation of both Ser473 and Thr308, which results in increased cell survival.
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Tsen, Guoshan. "Molecular characterization of a heparan sulfate proteoglycan that interacts with the neural cell adhesion molecule (NCAM) /." The Ohio State University, 1997. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487945320760721.
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Thwaites, Tristan. "Characterisation of the molecular basis underlying Chlamydial subversion of focal adhesion signaling." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/40508.
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Chlamydiae are obligate intracellular bacterial pathogens with medical and veterinary importance. Their principal virulence mechanism is their ability to invade different cell types both in vivo and in vitro. Whilst the human species, Chlamydia trachomatis and Chlamydia pneumoniea, are limited to infection of mucosal epithelium, the veterinary species of Chlamydia caviae, Chlamydia psittaci, Chlamydia abortus, amongst others, tend to establish a more systemic infection causing organ failure, reproductive defects, and spontaneous abortion. The cell invasion mechanism of Chlamydia trachomatis is the best studied, implicating the chlamydial protein TarP and, specifically, the N-terminal domain that is phosphorylated by the Src-family of non-receptor tyrosine kinases. The veterinary species also possess their respective TarP homologues, but they differ from the Chlamydia trachomatis version by lacking the N-terminal phosphodomain. To resolve this issue, and begin to elucidate the alternative invasion mechanism exhibited by the non-trachomatis species, a bioinformatics-based search of potential signalling motif within the highly conserved C-terminal half of TarP was performed. A candidate Vinculin Binding Domain (VBD) and Focal Adhesion Kinase (FAK)-binding motif (LD) were indentified, which were determined to function in recruiting vinculin and FAK to the sites of invasion, respectively. In addition, the VBD positively influenced the actin-recruiting function of the LD motif. Structural modelling revealed the formation of the hydrophobic interface in VBD/vinculin or LD/FAK interaction. Finally, knockout mouse embryonic fibroblasts confirmed a role for vinculin and FAK in invasion. Altogether, the data indicate that TarP-mediated exploitation of focal adhesion signalling represents a pan-chlamydial invasion mechanism. Interestingly, this signalling mechanism was found to have a post-invasion function. Chlamydia infection led to changes in focal adhesions and adherens junctions, which may be important in apoptosis resistance, counteracting the exfoliation cues provided by neighbouring cells, or cell motility and dissemination of infection within the host.
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Buckley, Christopher Dominic. "Molecular analysis of IgSF-integrin interactions : their role in leukocyte endothelial adhesion." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.320117.
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Qouta, Lolita Abdulla. "The biochemistry and molecular biology of intercellular adhesion in plant tissue culture." Thesis, University of Glasgow, 2008. http://theses.gla.ac.uk/302/.
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The adhesion between neighbouring plant cells is established as cells are formed during cytokinesis through the middle lamella that is made principally of pectins and proteins. Pectins are secreted into the cell wall in a highly methylesterified form and subsequently de-esterified in muro by pectin methyl esterase (PME, E.C. 3.1.11). The present study reports on the biochemical characterization and immunochemical analyses of phosphate buffer/EDTA pectic extracts associated with cell-cell adhesion in suspension cultures of wild type (WT), salt tolerant (HHS) cell lines and synchronized Arabidopsis suspension cultures. Using the synchronized cultures, The PME-mediated configuration of pectins at the onset of adhesion during cytokinesis, was assessed through the analysis of the expression patterns of the PME isoforms annotated to be expressed throughout the cell cycle The wild type Arabidopsis seemed to maintain the intercellular adhesion through the gelling of the highly methylated JIM7 recognized homogalacturonans that were shown to be abundant in the primary cell walls, middle lamellae and cellular junctions, possibly due to the hydrophobic interactions between the methoxy groups. The rhamnogalacturonan-I fraction was rich in arabinan side chains reflecting the proliferative state of the cells. The increase in arabinan content was accompanied by a reduction in the galactan content 4 days after subculturing. The cell walls of salt tolerant Arabidopsis contained the JIM7 and LM7recognized epitopes along with a high degree of branching of rhamnogalacturonan-I carrying galactans and arabinans as side chains. The change in the detected epitopes is thought to play a role in the ability of the cells to withstand the high osmotic pressure and increase the in the level of adhesion between cells. The JIM5 low methylesterified HGs were less abundant in both cultures, and the absence of the 2F4 antibody recognizing the Ca2+ egg boxes could be attributed to the scarce amounts of Ca2+ present in the culturing medium The immunochemical studies of the pectin extracted from the synchronized Arabidopsis suspension cultures after washing out aphidicolin indicated that the recognition of both of JIM7 and JIM5 varied in parallel during the cell cycle, whereas, the recognition of arabinan increased during the cell division. The sequence and phylogenetic analysis of ten PME isoforms that were annotated to be expressed at one or more phases of the cell cycle of synchronized Arabidopsis thaliana suspension cultures (Menges and Murray, 2002 and 2003), revealed that only five of these genes could be PMEs. The genes At4g02330, At1g02810, At2g26440, and At2g47550 were thought to be of type II PMEs which have a pre-pro-catalytic domains and At5g47500 is a type I PME that lack the pro-region. The amino acid sequence of At4g12390 showed similarities with the N-terminal pro-peptides of plant PME and invertase inhibitors. The expression of several PME genes was studied in suspension cultures of Arabidopsis thaliana synchronised using aphidicolin. Semi-quantitative PCR experiments showed that the expression of At5g47500 transcript was always detected during M phase of the cell cycle. The rest of the genes failed to show consistent patterns of expression. Northern blots revealed that mRNA coding for At5g47500 decreases during S and G2 phases and accumulates during the M phase of the cell cycle. Our results suggest that this PME isoform is involved in the modulations of the cell walls as the cells are going through division and cytokinesis.
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Newe, Abigail Lucy. "Unearthing the molecular mechanisms that govern L-selectin-dependent adhesion and migration." Thesis, King's College London (University of London), 2015. http://kclpure.kcl.ac.uk/portal/en/theses/unearthing-the-molecular-mechanisms-that-govern-lselectindependent-adhesion-and-migration(8f22370e-34b7-447f-98c2-dd1713036a84).html.
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L-selectin has been well characterised as a cell adhesion molecule, which plays a role in the recruitment of leukocytes to sites of inflammation and is responsible for the recirculation of lymphocytes to secondary lymphoid organs. Recent evidence has shown that L-selectin also acts as a signalling molecule to activate pathways and regulate the inflammatory response. The cytosolic tail of L-selectin plays a crucial role in regulating its activity through its interaction with binding partners, such as calmodulin (CaM) and the ERM protein family. However, little is known about how the interaction between L-selectin and its binding partners is regulated. The aim of this multidisciplinary PhD project is to use biophysical and cell biological methods to address the role of the interaction between L-selectin and its binding partners during leukocyte recruitment. To this end, the interaction between CaM and the L-selectin cytosolic tail was assessed using isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR) spectroscopy. Analysis revealed that phosphorylation of serine residues within the cytosolic tail of L-selectin did not affect CaM binding. To enable the observation of the interaction between L-selectin and CaM whilst leukocytes are undergoing transendothelial migration (TEM), the THP-1 monocytic cell line was engineered to stably express L-selectin-GFP and CaM-RFP so their interaction could be monitored at different stages of TEM. The data showed that phosphorylation of serine 364 in the L-selectin tail is important for regulating CaM interaction. Discrepancies were identified between the biophysical and cell biological results, implying the leukocyte plasma membrane may play a vital role in regulating the interaction between L-selectin and CaM. This highlights the importance of studying transmembrane proteins in the correct context.
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Strömberg, Nicklas. "Studies on receptor glycosphingolipids for bacterial adhesion molecular details as revealed by a novel solid phase assay /." Göteborg : Dept. of Medical Biochemistry and Faculty of odontology, University of Göteborg, 1988. http://books.google.com/books?id=gslpAAAAMAAJ.
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Chong, William Woei Fong. "Adhesive and molecular friction in tribological conjunctions." Thesis, Cranfield University, 2012. http://dspace.lib.cranfield.ac.uk/handle/1826/7160.
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This thesis investigates the underlying causes of friction and ine ciency within an
internal combustion engine, focusing on the ring-liner conjunction in the vicinity
of the power-stroke top dead centre reversal. In such lubricated contacts, friction
is the result of the interplay between numerous kinetics, with those at micro- and
nano-scale interactions being signi cantly di erent than the ones at larger scales.
A modi ed Elrod's cavitation algorithm is developed to determine the microscopic
tribological characteristics of the piston ring-liner contact. Predicting lubricant tran-
sient behaviour is critical when the inlet reversal leads to thin lms and inherent
metal-to-metal interaction. The model clearly shows that cavitation at the trailing
edge of the ring-liner contact generated pre-reversal, persists after reversal and pro-
motes starvation and depletion of the oil lm. Hence, this will lead to boundary
friction.
A fractal based boundary friction model is developed for lightly loaded asperity con-
tacts, separated by diminishing small lms, usually wetted by a layer of molecules
adsorbed to the tips of the asperities. In nano-scale conjunctions, a lubricant layering
e ect often takes place due to the smoothness of surfaces, which is governed by the
surface and lubricant properties. A molecularly thin layer of lubricant molecules can
adhere to the asperities, being the last barrier against direct surface contact. As a
result, boundary friction (prevailing in such diminishing gaps) is actually determined
by a combination of shearing of a thin adsorbed lm, adhesion of approaching as-
perities and their plastic deformation. A model for physio-chemical hydrodynamic
mechanism is successfully established, describing the formation of thin adsorbed
lms between asperities. This model is e ectively integrated with separately devel-
oped models that predict the adhesive and plastic contact of asperities.
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Liu, Qingde. "Molecular and physical determinants of fibrinogen-dependent platelet aggregation and adhesion in flow." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/NQ50213.pdf.
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Bohil, Aparna Bhaskar Cheney Richard E. "Myosin-X is a molecular motor central to filopodia formation, adhesion, and signaling." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2006. http://dc.lib.unc.edu/u?/etd,713.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2006.<br>Title from electronic title page (viewed Oct. 10, 2007). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Cell and Molecular Physiology - School of Medicine." Discipline: Cell and Molecular Physiology; Department/School: Medicine.
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Liu, Qingde 1963. "Molecular and physical determinants of fibrinogen-dependent platelet aggregation and adhesion in flow." Thesis, McGill University, 1998. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=35909.
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Fibrinogen (Fg) mediates platelet aggregation and adhesion to artificial surfaces by interacting with its receptor, glycoprotein IIb and IIIa complex (GPIIbIIIa, or integrin alphaIIbbeta 3), on the platelet membrane. Considerable evidence has demonstrated that the (H12) on the gamma chain carboxyl terminus is required for the binding of Fg from solution to activated platelet GPIIbIIIa, while the RGD sites, the universal integrin recognition domain on adhesive ligands, are not involved. In this study, using recombinant Fg, well-defined Fg plasmin digestion fragments, and specific monoclonal anit-Fg antibodies, we demonstrated that the same sequence, the H12, or more precisely, the AGDV on the extreme carboxyl terminus of the gamma chain (gamma408--411), is also required for platelet-bound Fg to support platelet aggregation (crosslinking), thus experimentally verifying the "two sticky ends" theory of Fg-mediated platelet aggregation The RGD-containing domains on the Aalpha chains are not involved in aggregation. The AGDV sequence on the gamma chain carboxyl terminus is also necessary and sufficient for activated platelets to adhere to surface-adsorbed Fg, while the RGD sequences we similarly not required. A receptor induced binding site (RIBS), the Fg RIBS-I site (gamma373--385), on Fg either bound to its GPIIbIIIa-receptor or on a surface, is not directly involved in interactions between platelet GPIIbIIIa and immobilized Fg. The inhibitory effects of the anti-Fg-RIBS-I antibody are due to steric hindrance of the accessibility of the AGDV site to platelet GPIIbIIIa. Thus, the extreme carboxyl terminus of the gamma chain is the only site in both fluid and solid phase Fg that is involved in platelet GPIIbIIIa-Fg interactions.<br>Though resting platelets are able to adhere to surface-bound Fg, this adhesion efficiency is much lower than that of the adhesion of the activated platelets. The adhesion efficiency of both resting and activated platelets to surface-adsorbed Fg decreases with increasing shear rate from 100 s -1 to 2,000 s-1. However, the decrease of the adhesion efficiency of the resting platelets is more marked than the decrease of the adhesion efficiency of the activated ones. Thus, the higher the shear rates, the larger the difference in the adhesion efficiencies between resting and activated platelets. However, due to the higher collision frequencies at higher shear rates, the adhesion of resting platelets was maintained at a similar level from shear rates of 300--2,000 s-1, while the adhesion of activated platelets kept increasing from 100 s -1 to 2,000 s-1. These data indicate that platelet activation is an efficient regulation pathway for platelet adhesion to surfaces.
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Thekke, Palasseri Vipin Madhavan. "Molecular Mechanisms Underlying Adhesion and Regulation of Virulence of Human Enterotoxigenic Escherichia coli." Thesis, Griffith University, 2016. http://hdl.handle.net/10072/367416.
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Enterotoxigenic Escherichia coli (ETEC) is the key etiological agent of traveller’s diarrhea. It accounts for 200 million cases of diarrhea and 380,000 deaths annually. ETEC uses proteinaceous appendages called pili in order to attach with host intestine, followed by secretion of enterotoxins leading to profuse diarrhea.
Among various ETEC pili that are characterised till date, CFA/I is the archetype of a class of pili called class 5 (α pili) pili. CFA/I is composed of two types of protein subunits. It consists of a cylindrical stalk of CfaB subunits and CfaE at the tip. Both intra and inter subunit bonding takes place via donor strand complementation. CfaE is widely accepted as an adhesin molecule that binds to human intestine and human erythrocytes. Also CfaE is regarded as nucleating molecule for pili synthesis (Li et al., 2007, Baker et al., 2009). An AraC family of transcriptional activator (AFTR), Rns is known to regulate CFA/I synthesis and another half of known ETEC pili. Present study focuses on three aspects of ETEC virulence.
First, Although CfaE is considered to be the key adhesin, an existing hypothesis claims that CfaB could independently bind to glycosphingolipid receptors, including asialo-GM1. Furthermore, it claims that CFA/I pili could be synthesised without CfaE (Jansson et al., 2006). Our studies indicate that, contrary to the existing model, CfaB does not bind asialo- GM1 independently of CfaE. Neither isolated CfaB subunits nor CfaB assembled into pili bind to asialo-GM1. Instead, we demonstrated that binding activity for asialo-GM1 resides in CfaE and is essential for pilus binding to intestinal epithelial cells. We concluded that the binding activities of CFA/I pili for asialo-GM1, erythrocytes and intestinal cells are inseparable, depend on the same amino acid residues in CfaE and therefore represent the same or very similar binding mechanisms.<br>Thesis (PhD Doctorate)<br>Doctor of Philosophy (PhD)<br>School of Medical Science<br>Griffith Health<br>Full Text
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Director, Laura Taylor. "A Novel Approach For The Identification of Cytoskeletal and Adhesion A-Kinase Anchoring Proteins." ScholarWorks @ UVM, 2014. http://scholarworks.uvm.edu/graddis/264.
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A-kinase anchoring proteins (AKAPs) are signaling scaffolds which provide spatial and temporal organization of signaling pathways in discrete subcellular compartments. Through tethering the cyclic-AMP dependent protein kinase A (PKA), AKAPs target PKA activity to distinct regions in the cell, bringing PKA in close proximity to its target proteins. This provides a high level of specificity and regulation of PKA and its role in mediating a number of biological processes, one of which is cell migration. Cell migration is a highly dynamic and fundamental process, when misregulated can lead to a number of pathologies. The process of cell migration requires integration and coordination of actin cytoskeletal dynamics, adhesion turnover, and contractility. The important role of PKA in regulating the cellular processes involved in cell migration has been extensively studied. Our lab has shown that PKA activity and spatial distribution through AKAPs are localized to the leading edge of migrating cells and are required for effective cell migration, yet the specific AKAPs responsible remain unknown.
Traditional methods for identifying AKAPs suffer from a number of limitations. Therefore the objective of the enclosed work is to establish and characterize a novel approach for the identification of cytoskeletal and adhesion-associated AKAPs. We show for the first time, an in vitro approach to identify cytoskeletal AKAPs which may be responsible for localizing PKA to the leading edge of migrating cells.
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Crabb, Edward B. "An Evaluation of Induced Shear Stress on Endothelial Cellular Adhesion Molecules." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5911.
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The pathophysiology of atherosclerotic cardiovascular disease (CVD) is highlighted by vascular dysfunction and low-grade vascular inflammation. Furthermore, the site-specific distribution of atherosclerosis throughout the arterial vasculature is primarily determined by local hemodynamic force. Therefore, this dissertation outlines three experiments designed to investigate the role of acute mental and physical (i.e., aerobic exercise), and vascular wall shear stress (SS) on the inflammatory aspects of atherosclerosis. Chapter 2 examines the effect of acute laboratory-induced mental stress on intracellular pro-inflammatory signaling pathways in peripheral blood mononuclear cells. Chapter 3 investigates the impact of acute laboratory-induced mental stress and maximal aerobic exercise on the concentration of soluble VCAM-1 (sVCAM-1) and CX3CL1/fractalkine (sCX3CL1) in human serum. Lastly, Chapter 4 examines the role of short- (30 min) and long-term (24 hr) low-to-negative oscillating SS (LOSS) and high laminar SS (HLSS) on the expression and secretion (i.e., cleavage) of cell-membrane VCAM-1 and CX3CL1 by human umbilical vein endothelial cell cultures in vitro. Together, these experiments provide evidence that acute psychological stress, maximal aerobic exercise, and HLSS influence vascular inflammation and adhesive properties of the vessel wall. More specifically, the results from Chapter 2 provide evidence that acute mental stress promotes the immune-cell mediated synthesis of pro-inflammatory cytokines in circulation. In addition, Chapter 3 and Chapter 4 demonstrate that the elevations in blood flow and hemodynamic force associated with maximal aerobic exercise, and unidirectional high SS may have the capacity to alter the expression of endothelial-bound cellular adhesion molecules, in part by eliciting their release from the vessel wall.
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Turaga, Soumya. "TUMOR CELL INTRINSIC AND EXTRINSIC FUNCTIONS OF JUNCTIONAL ADHESION MOLECULE-A (JAM-A) IN GLIOBLASTOMA." Cleveland State University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=csu1575548662111326.
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Ismail, Hodan. "Vascular endothelial growth factor and angiopoietin-1 regulate leukocyte adhesion to endothelial cells through the nuclear receptor Nur77." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107844.
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Vascular endothelial growth factor (VEGF) and angiopoietin 1 (Ang-1) are critical regulators of angiogenesis. Additionally, both have been found to participate in inflammatory processes: VEGF as a pro-inflammatory and Ang-1 as an anti-inflammatory mediator. Nur77 is a member of a family of orphan receptors (NR4A) that includes Nurr1 and Nor1 and plays a role in regulating vascular inflammation; however, this has yet to be fully understood. The aim of this study was to evaluate whether Nur77 expression in endothelial cells (ECs) serves as a negative feedback mechanism designed to inhibit NFkappaB induction, dampen VEGF-induced E-selectin and VCAM1 expression and enhanced leukocyte adhesion to ECs, and mediate the suppression of EC activation induced by Ang-1 treatment.Treatment of human umbilical vein endothelial cells (HUVECs) with either VEGF or Ang-1 significantly and transiently induced Nur77 expression and enhanced PKD-dependent HDAC7 phosphorylation and mobilization from the nucleus to the cytosol. HUVECs transduced with adenoviruses expressing mutated HDAC7 or a dominant-negative PKD1 inhibited VEGF-, but not Ang-1-, induced Nur77 expression. Inhibition of PI3K and ERK1/2 resulted in the suppression of Ang-1-induced Nur77 expression whereas the inhibition of JNK resulted in significantly greater induction of Nur77 by Ang-1. NFκB binding activity and gel shift assays revealed that Nur77 inhibits VEGF-induced NFκB activity. Overexpression of Nur77 showed titre-dependent upregulation of IκBα mRNA and protein expressions that was not evident in HUVECs transduced with viruses expressing a dominant-negative form of Nur77 (Ad-dnNur77). Functionally, Nur77 was found to suppress VEGF-induced mRNA and protein expressions of the adhesion molecules E-selectin and VCAM1. Importantly, the role of Nur77 in cytokine-induced leukocyte adhesion to ECs was examined. Adherence of U937 cells to HUVECs activated by VEGF was suppressed by overexpressing Nur77 whereas the loss of Nur77 by siRNA interference resulted in augmentation of adhesion. Interestingly, Ang1 was able to dampen VEGF-induced monocyte adhesion to HUVEC monolayers. I conclude that Nur77 plays an important role in providing a negative feedback mechanism designed to attenuate VEGF-induced pro-inflammatory responses through selective inhibition of NFκB activation. Furthermore, Nur77, in part, may be vital to the Ang-1 anti-inflammatory response.<br>Les facteurs de croissance endothélials vasculaires (VEGF) et l'angiopoïétine 1 (Ang-1) sont de régulateurs essentiels de l'angiogénèse. En outre, tous les deux ont été découverts pour leur participation dans le processus d'inflammation: VEGF comme pro-infammatoire et Ang-1 comme médiateur anti-inflammatoire. Nur77 est un membre de la famille des récepteurs orphelins (NR4A) qui comprend Nurr1 and Nor1 et jouent un rôle dans la régulation de l'inflammation vasculaire; toutefois cela n'est pas encore totalement compris. Le but de cette étude était d'évaluer si l'expression de Nur77 dans les cellules endothéliales (ECs) sert de mécanisme de rétroaction négatif conçu pour inhiber l'induction de NFκB en réduisant l'expression de la E-selectin et de VCAM1 induite par VEGF, ainsi que l'adhésion des leucocytes aux ECs, et pour agir en médiateur de la suppression de l'activation des ECs induite par le traitement avec Ang-1. Le traitement des cellules endothéliales humaines de la veine ombilicale (HUVECs) soit avec VEGF ou Ang-1 induit de façon significative et transitoire l'expression de Nur77 et augmente la Phosphorylation de HDAC7 PKD dépendante et la mobilisation du noyau vers le cytosol. Les HUVECs transduits avec les adénovirus exprimant HDAC7 muté ou un dominant négatif PKD1 inhibent VEGF, mais pas l'expression de Nur77 induit par Ang-1. L'inhibition de la PI3K et de ERK1/2 aboutit à la suppression de l'expression de Nur77 induit par Ang-1 alors que l'inhibition de JNK résulte de façon significative en une plus grande induction de Nur77 par Ang-1. L'essai d'activité de liaison de NFκB ainsi que celui du gel de retardation révèlent que Nur77 inhibe l'activité de NFκB induit par VEGF. La surexpression de Nur77 a montré une sur-régulation dépendante de la titration de l'ARNm et de l'expression protéique de IκBα, pas évidente avec les HUVECs transduites avec les virus exprimant la forme dominante négative de Nur77 (Ad-dnNur77). J'ai trouvé que Nur77 réprimait l'ARNm et l'expression protéique de E-selectin and VCAM1 induit par VEGF. De façon importante, le rôle de Nur77 dans l'adhésion des leucocytes aux ECs induits par les cytokines a été examiné. L'adhérence des cellules U937 aux HUVECs activées par VEGF était réprimée par la surexpression de Nur77 alors que la perte de Nur77 par l'ARNsi d'interférence résulte dans une augmentation de l'adhésion. De manière intéressante, Ang-1 était capable d'amortir l'adhésion aux monocouches de HUVECs induite par VEGF. Je conclus que Nur77 joue un rôle important en fournissant un mécanisme de rétroaction négatif conçu pour atténuer la réponse pro-infammatoire induite par VEGF à travers l'inhibition sélective de l'activation de NFκB. Par ailleurs Nur77 en partie, peut être vital pour les réponses anti-inflammatoires d'Ang-1.
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Dos, Santos Washington Luis Conrado. "Molecular characteristics of the endothelial cell surface : role in the control of lymphology adhesion." Thesis, King's College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283196.
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Copeman, Kayla. "Evaluating Epoxy Cure And Adhesion Strength Through Single-Sided Nmr Measurements Of Molecular Mobility." W&M ScholarWorks, 2021. https://scholarworks.wm.edu/etd/1627047854.
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Commonly used in aerospace, automotive, marine, defense, electronic, and manufacturing industries, epoxy adhesives offer advantages over mechanical joints by providing stronger and/or more flexible bonds, more uniform stress distribution, low shrinkage, and lightweight connections between materials. Determination of curing kinetics and properties of interfaces between epoxy and inorganic substrates provides insight that is useful for quality control and defect detection for such applications. Single-sided NMR provides a nondestructive and inexpensive method for probing epoxy materials and spatially resolving the decay of spin-lattice and spin-spin relaxation times (T1 and T2) during and after curing of epoxy resins onto substrates. In this thesis, we report the use of single-sided NMR for both characterizing the strength of adhesion between epoxy and inorganic substrates and monitoring the cure of epoxy at various temperatures. Multi-dimensional T1 –T2 measurements were performed to correlate with changes in surface energies that provide insight on the chemical adhesion of various epoxy samples. Furthermore, we used NMR measurements to monitor in-situ room-temperature and heat curing of epoxy to probe reductions in molecular mobility throughout the curing process. NMR relaxation properties were correlated with DSC data for comparison of the cure extent and cure rates. Our results show the efficacy of single-sided NMR measurements for studying curing, the extent of cure, adhesion strength of epoxies, and interphase phenomena.
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Cheng, Ling. "MOLECULAR MECHANISM OF L1CAM FUNCTION: AXON GROWTH AND GUIDANCE." Connect to online version, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1081281361.
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Kambe, Yusuke. "Molecular Design of Silk Fibroin for Functional Scaffolds." 京都大学 (Kyoto University), 2013. http://hdl.handle.net/2433/174922.
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Van, Order Jon P. "Molecular modeling of intermediate order in polymer glasses." Diss., Georgia Institute of Technology, 1999. http://hdl.handle.net/1853/10134.
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