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1
Choi, Mi-Yon. "P53 mediated cell motility in H1299 lung cancer cells." VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/109.
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Studies have shown that gain-of- function mutant p53, AKT, and NFκB promote invasion and metastasis in tumor cells. Signals transduced by AKT and p53 are integrated via negative feedback between the two pathways. Tumor derived p53 was also indicated to induce NFκB gene expression. Due to the close relationship between p53/AKT and p53/NFκB, we hypothesized that AKT and NFκB can enhance motility in cells expressing mutant p53. Effects on cell motility were determined by scratch assays. CXCL5- chemokine is also known to induce cell motility. We hypothesized that enhanced cell motility by AKT and NFκB is mediated, in part, by CXCL5. CXCL5 expression levels in the presence and absence of inhibitors were determined by qRT-PCR. We also hypothesized that gain-of-function mutant p53 contributes to the activation of AKT. The effect of mutant p53 on AKT phosphorylation was investigated with a Ponasterone A- inducible mutant cell line (H1299/R175H) and vector control. These results indicated that AKT and NFκB enhance motility in cells expressing mutant p53 and this enhanced motility is, in part, mediated by CXCL5. However, AKT phosphorylation was independent of mutant p53.
2
Bai, Limiao, and 白利苗. "In silico simulation of actin-based motility." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B46429116.
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Friedrich, Benjamin. "Chemotaxis of Sperm Cells." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2009. http://nbn-resolving.de/urn:nbn:de:bsz:14-ds-1235056439247-79608.
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Sperm cells are guided to the egg by chemoattractants in many species. Sperm cells are propelled in a liquid by the regular beat of their flagellum. In the presence of a concentration gradient of a chemoattractant, they can steer upwards the concentration gradient, a process called chemotaxis. Eggs release chemoattractants to guide the sperm cells to the egg. Sperm chemotaxis is best studied experimentally in the sea urchin. There, specific receptors in the flagellar membrane of the sperm cells are activated upon binding of chemoattractant molecules and trigger a signaling cascade which ultimately changes the activity of the molecular motors which drive the flagellar beat and result in a swimming response. Sea urchin sperm cells swim along circular and helical paths. Sperm cells of the sea urchin and several other species swim along helical paths far from boundary surfaces in the absence of chemoattractant. In a two-dimensional experimental geometry, sperm swimming paths are planar circles. The non-zero curvature of their swimming paths is a direct consequence of an asymmetry of their flagellar beat. In a concentration gradient of chemoattractant, sperm swimming path are drifting circles in two dimensions and bend helices in three dimensions. What is the working mechanism of sperm chemotaxis? In this thesis, we develop a theoretical description of sperm chemotaxis which can be subsumed as follows: While swimming along an approximately circular path in a concentration gradient a sperm cell traces a periodic concentration stimulus from the concentration field that has the frequency of circular swimming. The chemotactic signaling system processes this stimulus and causes a periodic modulation of the curvature of the swimming path which then gives rise to a swimming path which is a drifting circle. The relative direction of the drift with respect to the gradient direction is determined by the phase shift between the stimulus and the curvature oscillations. This picture is in perfect agreement with recent experimental findings. The mechanism is more general and also works in three dimensions for swimming along helical paths. Our results. Our theoretical description of sperm chemotaxis clarifies the concepts underlying sperm chemotaxis. In particular, we derive the role of internal timing of the chemotactic signaling system for sperm chemotaxis. We conclude that sampling a concentration field along circular and helical paths is a robust strategy for chemotaxis that does not require fine-tuning of parameters and which works reliable also in the presence of fluctuations. In a last chapter of this thesis, we discuss sperm chemotaxis in the more general context of an abstract search problem.
4
Thurston, Gavin O. "Studies on the effect of radiation on 3T3 cell motility." Thesis, University of British Columbia, 1988. http://hdl.handle.net/2429/29441.
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The ability of mammalian cells to locomote is important in a variety of normal and pathological processes. Previous work has suggested that low doses of x-irradiation may perturb cell motility, a finding that may have important consequences in embryogenesis, cancer metastasis, and immune response. This thesis has sought to study in more detail the effect of radiation on mammalian cell motility.
Work performed in other laboratories used the colloidal gold assay and time lapse cinemicroscopy to study x-irradiation induced changes to 3T3 fibroblast motility in tissue culture. These studies were repeated here, with qualitative results similar to those reported earlier. However, these methods were not amenable to a detailed quantitative analysis. For this, spatial and temporal information on the motility and dynamic morphology of a large number of cells is required. Such a task would be impossible to perform manually, thus an automated microscope system was developed that used a computer-driven precision stage and a solid state optical sensor to track individual cells in tissue culture. Information on motility and morphology was concurrently extracted from many cells. As part of the thesis, several techniques were developed to analyze and display these data, and to correlate motility and morphology observations. These techniques were directed at preserving the actual process of 3T3 cell motility, and parameters were measured to quantify the short term persistence of cell movement (on a time scale of 0.5 to 2 hours), and the long term persistence of cells in maintaining certain characteristic behaviour (on a time scale of 3 to 12 hours). The response of 3T3 fibroblasts to x-irradiation was characterized by a number of parameters. The population average cell speed was measured following treatment, and a dose response and time response was determined in the range of 1.5 Gy. Other motility parameters indicate that the normal process of cell motility, evidenced by a series of motile segments, was disrupted by x-rays. This was thought to reflect perturbation to the control mechanisms of cell motility.
The morphology of 3T3 cells stained with Coomassie blue was examined in an effort to correlate the observed motility changes with changes in the fixed cell morphology. This stain is a general structural protein stain with higher affinity toward microfilaments. High doses of x-rays were required to produce significant perturbation to cell morphology, and in the dose regime of interest, the morphology of irradiated cells was not identifiably different from control. Of note is that it was the well spread, quiescent cells that seemed least perturbed by large doses of irradiation.
In summary, x-rays apparently disrupt the normal process of cell motility. Several lines of evidence suggest that actively migrating cells are the most perturbed by irradiation. This work has developed techniques to quantify cell motility in a meaningful way, and to characterize the x-ray induced perturbations.<br>Science, Faculty of<br>Physics and Astronomy, Department of<br>Graduate
5
Yang, Lingyan. "The role of reduced-on random-motile (ROM) in the regulation of lung cancer cell migration and vesicle trafficking." Thesis, The University of Sydney, 2010. https://hdl.handle.net/2123/28847.
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Cancer is a complex disease, with over 100 different types and subtypes. Based on clinical features and biological properties, lung cancers can be separated into two major categories: non-small cell lung cancer and small cell lung cancer. In this study, we explore the function of the Reduced On-random Motile (ROM) protein in the regulation of non-small cell lung cancer cell migration and vesicle trafficking.
6
Friedrich, Benjamin. "Chemotaxis of Sperm Cells." Doctoral thesis, Technische Universität Dresden, 2008. https://tud.qucosa.de/id/qucosa%3A23708.
Full textAbstract:
Sperm cells are guided to the egg by chemoattractants in many species. Sperm cells are propelled in a liquid by the regular beat of their flagellum. In the presence of a concentration gradient of a chemoattractant, they can steer upwards the concentration gradient, a process called chemotaxis. Eggs release chemoattractants to guide the sperm cells to the egg. Sperm chemotaxis is best studied experimentally in the sea urchin. There, specific receptors in the flagellar membrane of the sperm cells are activated upon binding of chemoattractant molecules and trigger a signaling cascade which ultimately changes the activity of the molecular motors which drive the flagellar beat and result in a swimming response. Sea urchin sperm cells swim along circular and helical paths. Sperm cells of the sea urchin and several other species swim along helical paths far from boundary surfaces in the absence of chemoattractant. In a two-dimensional experimental geometry, sperm swimming paths are planar circles. The non-zero curvature of their swimming paths is a direct consequence of an asymmetry of their flagellar beat. In a concentration gradient of chemoattractant, sperm swimming path are drifting circles in two dimensions and bend helices in three dimensions. What is the working mechanism of sperm chemotaxis? In this thesis, we develop a theoretical description of sperm chemotaxis which can be subsumed as follows: While swimming along an approximately circular path in a concentration gradient a sperm cell traces a periodic concentration stimulus from the concentration field that has the frequency of circular swimming. The chemotactic signaling system processes this stimulus and causes a periodic modulation of the curvature of the swimming path which then gives rise to a swimming path which is a drifting circle. The relative direction of the drift with respect to the gradient direction is determined by the phase shift between the stimulus and the curvature oscillations. This picture is in perfect agreement with recent experimental findings. The mechanism is more general and also works in three dimensions for swimming along helical paths. Our results. Our theoretical description of sperm chemotaxis clarifies the concepts underlying sperm chemotaxis. In particular, we derive the role of internal timing of the chemotactic signaling system for sperm chemotaxis. We conclude that sampling a concentration field along circular and helical paths is a robust strategy for chemotaxis that does not require fine-tuning of parameters and which works reliable also in the presence of fluctuations. In a last chapter of this thesis, we discuss sperm chemotaxis in the more general context of an abstract search problem.
7
Garg, Ayush A. "Electromagnetic Fields Alter the Motility of Metastatic Breast Cancer Cells." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1563816767104018.
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Liu, Chenli, and 刘陈立. "Formation of novel biological patterns by controlling cell motility." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46541913.
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The Best PhD Thesis in the Faculties of Dentistry, Engineering, Medicine and Science (University of Hong Kong), Li Ka Shing Prize,2010-11<br>published_or_final_version<br>Biochemistry<br>Doctoral<br>Doctor of Philosophy
9
Dean, Seema. "Does the cytoskeleton manipulate the auxin-induced changes in structure and motility of the endoplasmic reticulum?" Thesis, University of Canterbury. School of Biological Sciences, 2004. http://hdl.handle.net/10092/5036.
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The variations in ER structure and motility under different stages of cell development remain largely unexplored. Here, I observe ER structure and the changes that take place in this structure over time in growing and non-growing live epidermal cells of the pea tendril. The ER was labelled by green fluorescent protein, fused to the KDEL-ER retention signal and confocal scanning laser microscopy was used to
localize the fluorescent signal. I found both the structure and motility of growing cells to be different to non-growing cells. The growing cells had a more open arrangement of the cortical ER, fewer lamellae and showed greater tubular dynamics, while the non-growing cells had a denser arrangement of the cortical ER network, with more lamellae and less tubular dynamics. Furthermore, these differences in the cortical ER structure and dynamics were due to growth as, the ER in non-growing cells showed characteristics similar to those seen in growing cells when these cells were induced to grow by the exogenous application of auxin. These changes in ER structure and dynamics were dependant on both the microtubules and actin cytoskeleton networks.
10
Ahmad, Omaima Farid. "The Role of Filamin A in Cell Motility, Adhesion and Invasion in Ovarian Cancer Cells." University of Toledo Honors Theses / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=uthonors1503407822068426.
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Di, Kaijun. "The role of Id-1 on the proliferation, motility and mitotic regulation of prostate epithelial cells." View the Table of Contents & Abstract, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38588985.
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12
Lane, Alison Briana. "Campylobacter jejuni motility is regulated by co-culture with epithelial cells." Online access for everyone, 2007. http://www.dissertations.wsu.edu/Thesis/Spring2007/a_lane_1050207.pdf.
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13
Ramsden, Amy Elizabeth. "Spatial Distribution and Motility of Salmonella- Containing Vacuoles within Host Cells." Thesis, Imperial College London, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.506440.
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Yu, Xiao. "Study of the Motility of Biological Cells by Digital Holographic Microscopy." Scholar Commons, 2014. https://scholarcommons.usf.edu/etd/5159.
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In this dissertation, I utilize digital holographic microscopy (DHM) to study the motility of biological cells. As an important feature of DHM, quantitative phase microscopy by digital holography (DH-QPM) is applied to study the cell-substrate interactions and migratory behavior of adhesive cells. The traction force exerted by biological cells is visualized as distortions in flexible substrata. Motile fibroblasts produce wrinkles when attached to a silicone rubber film. For the non-wrinkling elastic substrate polyacrylamide (PAA), surface deformation due to fibroblast adhesion and motility is visualized as tangential and vertical displacement. This surface deformation and the associated cellular traction forces are measured from phase profiles based on the degree of distortion. Intracellular fluctuations in amoeba cells are also analyzed statistically by DH-QPM. With the capacity of yielding quantitative measures directly, DH-QPM provides efficient and versatile means for quantitative analysis of cellular or intracellular motility.
Three-dimensional profiling and tracking by DHM enable label-free and quantitative analysis of the characteristics and dynamic processes of objects, since DHM can record real-time data for micro-scale objects and produce a single hologram containing all the information about their three-dimensional structure. Here, I utilize DHM to visualize suspended microspheres and microfibers in three dimensions, and record the four-dimensional trajectories of free-swimming cells in the absence of mechanical focus adjustment. The displacement of microfibers due to interactions with cells in three spatial dimensions is measured as a function of time at sub-second and micrometer levels in a direct and straightforward manner. It has thus been shown that DHM is a highly efficient and versatile means for quantitative tracking and analysis of cell motility.
15
Cao, T. "ROLE OF GANGLIOSIDES IN MODULATING THE MOTILITY OF HUMAN CANCER CELLS." Doctoral thesis, Università degli Studi di Milano, 2013. http://hdl.handle.net/2434/217448.
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Glycosphingolipids, due to their tendency to form laterally separated liquid-ordered phases, possess a high potential for the creation of order in biological membranes. The formation of glycosphingolipid-rich membrane domains within the membrane has profound consequences on the membrane organization at different levels, and on the conformational and biological properties of membrane-associated proteins and multimolecular protein complexes.
Alterations in the structures of carbohydrate epitopes associated with glycosphingolipids are a common feature of tumors and tumor cells (“aberrant glycosylation”). In particular, tumors are characterized by the peculiar ability to manipulate sialylation processes (1). This abnormal sialylation process generates peculiar antigenic determinants, which are normally absent in healthy cells, and affects cell homeostasis, altering the normal signaling pathways. Indeed, glycosphingolipids in tumor cells have been implicated in the regulation of cell adhesion, motility, recognition, survival and proliferation (2). Thus, an ever-increasing interest to this regard is being devoted to gangliosides, sialic acid-containing glycolipids, and to the enzymes affecting sialylation. Both sialyltransferases and sialidases seem to be involved in the phenomenon of aberrant sialylation in tumor cells.
The genetic (stable overexpression sialyltransferase I - SAT-I or GM3 synthase) or pharmacological (selective pressure by N-(4-hydroxyphenyl)retinamide)) manipulation of A2780 human ovarian carcinoma cells allowed us to obtain monoclonal cells characterized by higher GM3 synthase activity respect to wild type cells (3-5). High GM3 synthase expression resulted in 1) elevated ganglioside levels, 2) reduced in vitro cell motility and increased adhesion to fibronectin, 3) enhanced expression of the membrane adaptor protein caveolin-1, an integral membrane protein playing multiple roles as negative regulator in the progression of several types of human tumors (6,7).
Administration of exogenous gangliosides was able to strongly reduce in vitro cell motility and to increase cell adhesive ability to fibronectin in wild type cells, which are low GM3 synthase-expressing A2780 cells. Conversely, in high GM3 synthase-expressing clones, ganglioside depletion by treatment with the glucosylceramide synthase inhibitor D-PDMP was able to strongly increase cell motility and to reduce adhesion. In these cells, transient silencing of caveolin-1 by siRNA also led to increased motility. Thus, high levels of caveolin-1 and high levels of gangliosides are necessary, but not sufficient, if independent, to down-regulate tumor cell motility.
Treatment of A2780 cells with exogenous gangliosides only slightly increased the expression of caveolin-1; on the other hand it markedly increased the phosphorylation of caveolin-1 at tyrosine 14. Conversely, ganglioside depletion in high GM3 synthase-expressing clones by D-PDMP treatment markedly reduced caveolin-1 phosphorylation. These data suggest that phosphorylation of caveolin-1, rather than caveolin-1 total level, is controlled by gangliosides and is crucial in the control of tumor cell motility.
The non-receptor tyrosine kinase c-Src plays a crucial role in controlling the motility of these cells. In fact, 1) the motility of low GM3 synthase-expressing cells was reduced in the presence of a Src inhibitor; 2) c-Src was less active in high GM3 synthase-expressing clones; 3) D-PDMP treatment of high GM3 synthase-expressing cells led to c-Src activation, while gangliosides administration in wild type cells, low GM3 synthase-expressing A2780 cells reduced c-Src kinase activity.
In high GM3 synthase-expressing cells, caveolin-1 and gangliosides were highly enriched in detergent-resistant membrane fractions (DRM) prepared in the presence of Triton X-100. In the presence of D-PDMP treatment, the distribution of several lipids in sucrose gradient changed, followed by a shift of both caveolin-1 and c-Src from DRM fraction to intermediate fraction. However, integrins, which are receptors that mediate attachment between cells moved from high density fraction to DRM and intermediate fraction.
All of these data suggest a novel role of gangliosides in regulating tumor cell motility, by affecting the organization of a signaling complex organized by caveolin-1, responsible for Src inactivation downstream to integrin receptors, and imply that GM3 synthase is a key target for the regulation of cell motility and adhesion in human ovarian carcinoma.
16
Bratt, Anders. "The role of angiomotin in endothelial cell motility and cell-cell junction formation /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-479-1/.
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Tian, Jing. "Inhibition of melanoma cell motility by the snake venom disintegrin eristostatin." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 61 p, 2007. http://proquest.umi.com/pqdweb?did=1397900451&sid=10&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Fu, Xiongfei, and 傅雄飞. "Quantitative study of pattern formation on a density-dependent motility biological system." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B48199424.
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Quantitative biology is an emerging field that attracts intensive research interests.
Pattern formation is a widely studied topic both in biology and physics.
Scientists have been trying to figure out the basic principles behind the fascinating
patterns in the nature. It’s still difficult to lift the complex veil on the
underling mechanisms, especially in biology, although lots of the achievements
have been achieved. The new developments in synthetic biology provide a different
approach to study the natural systems, test the theories, and develop
new ones. Biological systems have many unique features different from physics
and chemistry, such as growth and active movement. In this project, a link
between cell density and cell motility is established through cell-cell signaling.
The genetic engineered Escherichia coli cell regulates its motility by sensing
the local cell density. The regulation of cell motility by cell density leads to
sequential and periodical stripe patterns when the cells grow and expand on a
semi-solid agar plate. This synthetic stripe pattern formation system is quantitative
studied by quantitative measurements, mathematical modeling and
theoretical analysis.
To characterize the stripe pattern, two novel methods have been developed
to quantify the key parameters, including cell growth, spatiotemporal cell density
profile and cell density-dependent motility, besides the standard molecular
biological measurements.
To better understand the underlying principle of the stripe pattern formation,
a quantitative model is developed based on the experiments. The detailed
dynamic process is studied by computer simulation. Besides, the model predicts
that the number of stripes can be tuned by varying the parameters in
the system. This has been tested by quantitatively modulation of the basal
expression level of a single gene in the genetic circuit.
Moreover, theoretical analysis of a simplified model provides us a clear picture
of the stripe formation process. The steady state traveling wave solution
is obtained, which leads to an analytic ansatz that can determine the phase
boundary between the stripe and the no-stripe phases.
This study does not only provide a quantitative understanding about the
novel mechanism of stripe pattern formation, but also sets an good example
of quantitative studies in biology. The techniques, methods and knowledge
gleaned here may be applied in various interdisciplinary fields.<br>published_or_final_version<br>Physics<br>Doctoral<br>Doctor of Philosophy
19
Batista, José Miguel Sebastiao Fernandes. "FAM49 : a novel regulator of the protrusive behaviour and motility of cells." Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7690/.
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Most eukaryotic cell motility relies on plasma membrane protrusions, which depend on the actin cytoskeleton and its tight regulation. The SCAR/WAVE complex, a pentameric assembly comprising SCAR/WAVE, Nap1, CYFIP/Pir121, Abi and HSPC300, is a key driver of actin-based protrusions such as pseudopods. SCAR/WAVE is thought to activate the Arp2/3 complex, a crucial actin nucleator, after being itself activated by upstream signals such as active Rac1. Despite recent progress on the study of the SCAR/WAVE complex, its regulation is still incompletely understood, with Nap1’s role being particularly enigmatic. Upon screening for potential Nap1 binding partners in the social amoeba Dictyostelium discoideum – a well established model organism in the study of the actin cytoskeleton and cell motility – we found FAM49, a ~36 kDa protein of unknown function which is highly conserved in Metazoa (animals) and evolutionarily closer species such as D. discoideum. Interestingly, D. discoideum’s FAM49 and its homologs contain a DUF1394 domain, which is also predicted in CYFIP/Pir121 proteins and most likely involved in their direct binding to active Rac1, which in turn contributes to SCAR/WAVE’s activation. FAM49’s unknown role, apparent high degree of conservation and potential connections to SCAR/WAVE and Rac1 persuaded us to start investigating its function and biological relevance in D. discoideum, leading to the work presented in this thesis. Several pieces of our data collectively support a function for FAM49 in modulating the protrusive behaviour, and ultimately motility, of D. discoideum cells, as well as a regulatory link between FAM49 and Rac1. FAM49’s involvement in protrusion regulation was first hinted at by our observation that GFP-tagged FAM49 is enriched in pseudopods. The possibility of a link with Rac1 was then strengthened by two additional observations: first, pseudopodial GFP-FAM49 is substantially co-enriched with active Rac, both showing fairly comparable spatio-temporal accumulation dynamics; second, when dominant-active (G12V) Rac1 is expressed in cells, it triggers the recruitment and persistent accumulation of GFP-FAM49 at the plasma membrane, where both become highly co-enriched. We subsequently determined that fam49 KO cells differ from wild-type cells in the way they protrude and move, as assessed in under-agarose chemotaxis assays. In particular, our data indicate that fam49 KO cells tend to display a lower degree of global protrusive activity, their protrusions extend more slowly and are less discrete, and the cells end up moving at lower speeds and with higher directional persistence. This phenotype was substantially rescued by FAM49 re-expression. While re-expressing FAM49 in fam49 KO cells we generated putative FAM49 overexpressor cells; compared to wild-type cells, they displayed atypically thin pseudopods and what seemed to be an excessively dynamic, and perhaps less coordinated, protrusive behaviour. Additional data in our study suggest that pseudopods made by fam49 KO cells are still driven by SCAR/WAVE, which is clearly not being replaced by WASP (as is now known to be the case in D. discoideum cells lacking a functional SCAR/WAVE complex). Nonetheless, the peculiar dynamics of those pseudopods imply that SCAR/WAVE’s activity is regulated differently when FAM49 is lost, though it remains to be determined how. This thesis is the first report of a dedicated study on FAM49 and lays the foundation for future research on it.
20
Wright, Adele Hart. "The role of integrins in the differential upregulation of tumor cell motility by endothelial extracellular matrix proteins." Diss., Georgia Institute of Technology, 1999. http://hdl.handle.net/1853/17352.
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Di, Kaijun, and 狄凱軍. "The role of Id-1 on the proliferation, motility and mitotic regulationof prostate epithelial cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B38944704.
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Seller, Zerrin. "Role of #alpha#4#beta#1-mediated signalling in malignant melanoma adhesion and motility." Thesis, King's College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266520.
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Hadjisavas, Michael. "Induction of mitogenesis and cell-cell adhesion by porcine seminal plasma." Title page, contents and abstract only, 1992. http://web4.library.adelaide.edu.au/theses/09PH/09phh1293.pdf.
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Includes list of publications by the author. Includes bibliographical references (leaves 103-123) Evaluates the nature of the interactions occurring between semen and cells of the uterus that occur following mating in pigs. Describes a novel ability of porcine seminal plasma to induce dose dependent cell-cell adhesion and mitogenesis amongst peripheral blood lymphocytes in vitro.
24
Chon, John H. "Characterization of single-cell movement using a computer-aided fluorescence time-lapse videomicroscopy system : role of integrins in endothelial cell migration." Thesis, Georgia Institute of Technology, 1996. http://hdl.handle.net/1853/11171.
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MITONAKA, Tomoaki, Yoshiyuki MURAMATSU, Shin SUGIYAMA, Tomoaki MIZUNO, and Yasuyoshi NISHIDA. "Essential roles of myosin phosphatase in the maintenance of epithelial cell integrity of Drosophila imaginal disc cells." Elsevier, 2007. http://hdl.handle.net/2237/9388.
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Adla, Shalini. "Characterization of the neural cell recognition molecule L1 in breast cancer cells and its role in breast cancer cell motility." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 125 p, 2008. http://proquest.umi.com/pqdweb?did=1459905751&sid=5&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Chen, Helen Hong. "Finite element-based computer simulation of motility, sorting, and deformation in biological cells." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0012/NQ30595.pdf.
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Halpern, David Carlos Mohrer Judice. "The squeezing of red blood cells through tubes and channels of near-critical dimensions." Diss., The University of Arizona, 1989. http://hdl.handle.net/10150/184839.
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The aim of this dissertation is to develop theoretical models for the motion of rigid and flexible particles through very tight spaces. The geometries of conduits which will be investigated are cylindrical tubes, parallel plane walls and rectangular channels. This work is motivated by an interest in the flow and deformation of single red blood cells in very narrow capillaries, in spleen and in bone marrow. Mammalian red cells are highly flexible, but their deformations satisfy two significant constraints. They must deform at constant volume, because the contents of the cell are incompressible, and also at nearly constant surface area, because the red cell membrane strongly resists dilation. Consequently, there exists a minimal tube diameter below which passage of intact cells is not possible. A cell in a tube with this diameter has its critical shape: a cylinder with hemispherical ends. The motion of red cells is analysed using lubrication theory. When the tube diameter is slightly larger than the minimal value, the cell shape is close to its shape in the critical case. However, the rear end of the cell becomes flattened and then concave with a relatively small further increase in the diameter. The changes in cell shape and the resulting rheological parameters are analysed using matched asymptotic expansions for the high-velocity limit and using numerical solutions. A rapid decrease in the apparent viscosity of red cell suspensions with increasing tube diameter is predicted over the range of diameters considered. The red cell velocity is found to exceed the mean bulk velocity by an amount which increases with increasing tube diameter. The same type of analysis is applied to the flow and deformation of red blood cells between two parallel plates with near-minimal spacings. First, the critical shape of the particle and the minimum gap width are determined using calculus of variations. In this case, it is a disk with a rounded edge. The flow in the plasma layers between the cell and the plates is described using lubrication theory. Approximate solutions can be obtained using a locally two-dimensional analysis at each point of the rim of the cell. Cell shapes, pressure distributions, membrane stresses and particle velocities are deduced as functions of geometrical parameters. One significant finding is that the gap width between the cell and the wall decreases with distance from the axis of symmetry parallel to the flow direction. The red cell velocity may be smaller or larger than the mean fluid velocity far from the cell, depending on the spacing of the plates, with equality when the width of the red cell is about ninety percent of the spacing between plates. The same procedure is also applied to rectangular channels.
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Tam, Wing-hei Winky, and 譚詠曦. "Adrenomedullin in oviduct and sperm function." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39430248.
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Daher, Jalil. "Exposure of endothelial cells to physiological levels of myeloperoxidase modified LDL delays pericellular fibrinolysis and reduces cell motility." Doctoral thesis, Universite Libre de Bruxelles, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209337.
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Cardiovascular diseases are considered the first cause of death in westernized societies. They are directly linked to atherosclerosis, a clinical condition characterized by a thickening of the arterial wall. Atherosclerosis is in his turn linked to various genetic and environmental factors; among those factors are high oxidized LDL levels and endothelial dysfunction. In the present study, we have analyzed in vitro the effect of myeloperoxidase oxidized LDL on endothelial cells at the level of fibrinolysis and cell motility.<p>In the first part of the work, we measured fibrinolysis in real time at the surface of endothelial cells. Our results suggest that myeloperoxidase oxidized LDL interferes with the regulation of fibrinolysis by endothelial cells by decreasing their pro-fibrinolytic activity. This effect was not related to a modification in expression of major regulators of fibrinolysis such as PAI-1 and t-PA. Our data link the current favorite hypothesis that oxidized LDL has a causal role in atheroma plaque formation with an old suggestion that fibrin may also play a causal role. A model that best explains our results would be as follows: oxidized LDL increases fibrin deposition on endothelial cells which will increase their permeability resulting in more oxidized LDL infiltration into the subendothelial space of the arterial wall initiating atherogenesis. <p>In the second part of the work, we investigated the effect of myeloperoxidase oxidized LDL at the level of endothelial cell motility. We have shown that oxidized LDL is able to decrease cell migration, wound healing and tubulogenesis in endothelial cells. Those effects were not associated with any alteration at the level of neither cell viability nor proliferation. Subsequent gene expression analyses enabled us to link the oxidized LDL induced phenotypical changes in the cells to a change in expression of both microRNA-22 and Heme Oxygenase 1 genes. Our observations suggest a novel role of oxidized LDL not only as an important factor in the initiation of atheromatous lesions, but also as a potential player in the progression of the atherosclerosis disease by impeding blood vessel repair and wound healing at the sites of lesions.<p><br>Doctorat en Sciences<br>info:eu-repo/semantics/nonPublished
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McCorkle, Joseph Robert. "NM23-H1 BLOCKS CELL MOTILITY INDEPENDENTLY OF ITS KNOWN ENZYMATIC ACTIVITIES IN A COHORT OF HUMAN MELANOMA CELLS." UKnowledge, 2010. http://uknowledge.uky.edu/gradschool_diss/84.
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The metastasis suppressor gene NM23-H1 has been shown to possess three enzymatic activities including nucleoside diphosphate kinase, histidine-dependent protein kinase and 3’-5’ exonuclease activity. While these properties have been demonstrated in vitro using recombinant proteins, the contribution of these activities to suppression of metastatic dissemination is unknown. Site-directed mutagenesis studies were used to identify amino acid residues which are required for proper function of each enzymatic activity associated with H1, providing a platform for studying the importance of each function on an individual basis. To assess the relevance of these activities to melanoma progression, a panel of mutants harboring selective lesions disrupting the enzymatic activities of H1 were overexpressed using stable transfection in two melanoma cell lines, WM793 (isolated from a vertical growth phase human melanoma), and the metastatic derivative cell line 1205LU. In vitro correlates of metastasis measuring motility and invasion were used in an attempt to identify the mechanism mediating H1-dependent motility suppression of cancer cells. Surprisingly, all mutants studied retained full motility suppression in this setting, suggesting that the enzymatic functions associated with H1 are not required for inhibiting cell migration. Instead, gene expression analyses conducted on the panel of stable transfectants indicate that differences in steady-state mRNA levels of genes involved in mitogen-activated protein kinase (MAPK) signaling showed significant correlations with H1 expression and motility suppression. RNAi studies have confirmed that H1-dependent modulation of the expression of two genes in particular, BRAP and IQGAP2, contribute to the observed phenotype, suggesting a novel mechanism used by NM23 to control cellular migration in human melanoma.
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Hoppe, Andreas. "Adaptive spline method for the assessment of cell motility and its application to lesions." Thesis, University of South Wales, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341937.
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McBride, Jared Adam. "Steady State Configurations of Cells Connected by Cadherin Sites." BYU ScholarsArchive, 2016. https://scholarsarchive.byu.edu/etd/6023.
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Many cells employ cadherin complexes (c-sites) on the cell membrane to attach to neighboring cells, as well as integrin complexes (i-sites) to attach to a substrate in order to accomplish cell migration. This paper analyzes a model for the motion of a group of cells connected by c-sites. We begin with two cells connected by a single c-site and analyze the resultant motion of the system. We find that the system is irrotational. We present a result for reducing the number of c-sites in a system with c-sites between pairs of cells. This greatly simplifies the general system, and provides an exact solution for the motion of a system of two cells and several c-sites.Then a method for analyzing the general cell system is presented. This method involves 0-row-sum, symmetric matrices. A few results are presented as well as conjectures made that we feel will greatly simplify such analyses. The thesis concludes with the proposal of a framework for analyzing a dynamic cell system in which stochastic processes govern the attachment and detachment of c-sites.
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Yang, Hong. "INVESTIGATIONS ON THE ROLE OF INTEGRINS IN ANOIKIS AND MOTILITY OF LUNG ADENOCARCINOMA CELLS." Scholarly Commons, 2008. https://scholarlycommons.pacific.edu/uop_etds/3090.
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The role of integrins in various aspects of tumor biology including tumor growth, angiogenesis, invasion and metastasis is well established. However, the integrin-specific involvement in these processes in non-small cell lung cancer (NSCLC) cells has not been thoroughly investigated. This study focuses on the role of integrins in cell motility and anoikis in NSCLC with an in vitro model system using the lung adenocarcinoma cell line A549 and its paclitaxel resistant derivative A549-T24. This research includes the following three parts:
In order to demonstrate whether stimulation of the signaling mediated through specific integrins can differentially sensitize A549 and T24 cells to anchorage dependent apoptosis (anoikis), flow cytometry was used to detect the percentage of cells in certain apoptotic stages. T24 cells treated with an antibody to αvβ3 integrin showed more early apoptosis than A549 treated with the same anti-integrin antibody.
To determine the involvement of integrins in mediating the motility of A549 and T24 cells, μ-slide chemotaxis chambers was used to detect chemotactic responses of migrating cells with or without treatment with anti-αvβ3 integrin. When treated with the antibody, both T24 and A549 cells attach less and move slower compared to untreated cells. In addition, the anti-integrin antibody caused a greater reduction of velocity of cell movement in T24 cells compared with A549 cells.
To understand the survival signaling pathway activated by specific integrin extracellular matrix (ECM) interactions, a western blot analysis was performed to demonstrate that the PI3K pathway was involved in integrin-ECM interactions inactivating BAD for cell survival in T24 cells.
Overall, specific integrin modulation in T24 cells resistant to paclitaxel may acquire some of their more-aggressive characteristics including rescuing from anoikis and accelerating cell movement.
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Xie, X. "GANGLIOSIDE-DEPENDENT MEMBRANE ORGANIZATION CONTROLLING THE ADHESION AND MOTILITY OF HUMAN OVARIAN CANCER CELLS." Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/246740.
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Glycosphingolipids, due to their tendency to form laterally separated liquid-ordered phases, possess a high potential for the creation of order in biological membranes. The formation of glycosphingolipid-rich membrane domains within the membrane has profound consequences on the membrane organization at different levels, and on the conformational and biological properties of membrane-associated proteins and multimolecular protein complexes (1).
Glycosphingolipids modulate several signal transduction processes controlling cell proliferation, survival, differentiation, and transformation. Since alterations in the expression of carbohydrate epitopes associated with glycosphingolipids are frequent in tumors, it has been hypothesized that glycosphingolipids could play important roles in modulating some of the properties of tumor cells. In fact, some tumors are characterized by the ability to manipulate sialylation processes determining the formation of antigenic determinants resulting from an “aberrant glycosylation” and affecting cell homeostasis, altering the normal signaling pathways (2). Thus, an ever-increasing interest to this regard is being devoted to gangliosides, sialic acid-containing glycolipids, and to the enzymes affecting sialylation. Both sialyltransferases and sialidases seem to be involved in the phenomenon of aberrant sialylation in tumor cells.
The genetic (stable overexpression of sialyltransferase I - SAT-I or GM3 synthase) or pharmacological (selective pressure by N-(4-hydroxyphenyl)retinamide) manipulation of A2780 human ovarian carcinoma cells allowed us to obtain monoclonal cells characterized by higher GM3 synthase activity respect to wild type cells (3-5). High GM3 synthase expression resulted in 1) elevated ganglioside levels, 2) reduced in vitro cell motility and increased adhesion to fibronectin, 3) enhanced expression of the membrane adaptor protein caveolin-1, an integral membrane protein playing multiple roles as negative regulator in the progression of several types of human tumors (6,7). The correlation between high ganglioside levels and decreased motility/increased adhesion were confirmed through administration of exogenous gangliosides which was not only able to strongly reduce in vitro cell motility, but also to significantly increase cell adhesive ability to fibronectin in wild type cells, low GM3 synthase expressing A2780 cells. Furthermore, in high GM3 synthase expressing clones, such as A2780/SAT-I cells, ganglioside depletion by treatment with the glucosylceramide synthase inhibitor D-PDMP was able to strongly reduce adhesion and to increase cell motility.
The α5β1 integrin, which mediates cell adhesion, is the most expressed integrin heterodimers in A2780 cells. Since fibronectin is the preferential ligand of integrin α5β1, it has been hypothesized that this integrin heterodimer might be involved in the regulation of adhesion and motility in human ovarian carcinoma cells. On the other hand, A2780/SAT-I cells also showed an increased adhesion to laminin and vitronectin suggesting a possible role of their respective integrin receptors in the regulation of GM3-mediated adhesion.
The role of a glycosphingolipid/caveolin-1 signaling complex in the negative regulation of A2780 cells motility has been reported, showing that high levels of caveolin-1 and high levels of gangliosides are necessary, but not sufficient, to down-regulate tumor cell motility (5). In GM3 synthase expressing cells, caveolin-1 and gangliosides were highly enriched in detergent-resistant membrane fractions (DRM) prepared in the presence of Triton X-100. D-PDMP treatment determined changes in the lipid distribution of several lipids in sucrose gradient fractions, and also altered protein distribution determining a shift of both caveolin-1 and c-Src, also involved in the previously mentioned complex signaling pathway, from the DRM fraction to intermediate fraction. Integrins, particularly α5 and β1 integrin subunits, following ganglioside depletion move from the high density fraction to DRM and intermediate fractions. D-PDMP treatment also affected protein association with caveolin-1, determining an increased association of this protein, a potential molecular organizer, with integrin subunits α5 and β1 without affecting the total level of proteins.
The in vitro adhesion of A2780/SAT-I cells was markedly higher in caveolin-1 silenced cells compared with scramble sequence transfected cells, suggesting a leading role of caveolin-1 in the regulation of the cell adhesion signal in this cell model. On the other hand, treatment of A2780 cells with exogenous gangliosides only slightly increased the expression of caveolin-1; while it markedly increased the phosphorylation of caveolin-1 at tyrosine 14. Conversely, ganglioside depletion in high GM3 synthase-expressing clones by D-PDMP treatment markedly reduced caveolin-1 phosphorylation. These data suggest that phosphorylation of caveolin-1, rather than caveolin-1 total level, is controlled by gangliosides and is crucial in the control of tumor cell adhesion.
These data suggest a novel role of gangliosides in regulating tumor cell adhesion and motility, by affecting the organization of a signaling complex organized by caveolin-1, and imply that GM3 synthase is a key target for the regulation of cell motility and adhesion in human ovarian carcinoma.
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Peterson, Joanne Lykins. "The effects of replicative senescence and telomerase on contraction and motility of fibroblasts /." Read thesis online, 2009. http://library.uco.edu/UCOthesis/PetersonJL2009.pdf.
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Gerasimcik, Natalija. "Activation, adhesion and motility of B lymphocytes in health and disease." Doctoral thesis, Stockholms universitet, Institutionen för molekylär biovetenskap, Wenner-Grens institut, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-92944.
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B cells can be activated by T cell-dependent stimuli, such as CD40 ligation and cytokines, which induce extensive proliferation, class switch recombination and somatic hypermutation. Epstein-Barr virus (EBV) can also induce B cell activation by mimicking T cell help through its main oncoprotein, latent membrane protein 1 (LMP-1). It is regulated by another EBV-encoded protein, EBV nuclear antigen 2 (EBNA-2), which is absent in Hodgkin and Burkitt lymphomas. We have studied LMP-1 induction by cytokines in vitro and shown that LMP-1 is induced through the transcription factor signal transducer and activator of transcription (STAT6) and a newly defined high-affinity STAT6-binding site. When IL-4 is added together with lipopolysaccharide (LPS) or α-CD40 to B cells, it induces homotypic round and tight aggregates in vitro, whereas LPS alone does not induce such morphological changes. I describe here attempts to identify the molecules that regulate these responses. I have shown that the Rho GTPase Cdc42 controls the spreading of B cells, whereas two other molecules in the same family, Rac1 and Rac2, control homotypic adhesion. Further, I have shown by conditional deletion of Cdc42 in B cells that it is important in the humoral immune response. Dock10 is a guanosine nucleotide exchange factor (GEF) for Cdc42. It is expressed through all differentiation stages of B cell development. However, targeted deletion of Dock10 in B cells does not result in an aberrant phenotype. Furthermore, by studying conditional knockout mice for Dock10, Cdc42, Rac1 and Rac2, I have elucidated the mechanism of cytoskeletal changes during B cell activation, leading to adhesion and motility. My results may lead to a better understanding of normal B cell activation and of EBV infection, which is associated with many human tumours and may help to understand cancer development and progression in B cells.<br><p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 3: Manuscript.</p>
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Weatherly, Kathleen. "Etude du rôle joué par la molécule S100A4 dans la différenciation et la fonction des lymphocytes T." Doctoral thesis, Universite Libre de Bruxelles, 2015. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209038.
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Pour lutter efficacement contre une attaque, l’organisme est doté d’un système immunitaire lui permettant de reconnaître le danger et de se défendre contre celui-ci. Les lymphocytes T jouent le rôle de chef d'orchestre de la réponse immunitaire, organisant l'activité des autres cellules nécessaires à la défense contre les infections. Pour accomplir ce rôle, les cellules T sont dotées d’une forte mobilité, leur permettant ainsi de circuler constamment dans diverses régions de l’organisme et d’y établir de nombreuses interactions.<p><p>Durant ce travail, nous nous sommes intéressé aux mécanismes moléculaires responsables de la motilité des cellules T. En particulier, nous avons investigué le rôle de la protéine S100A4, dont l’expression a été démontrée au sein de cellules T, dans la motilité de ces cellules ainsi que son implication dans l’inflammation. La protéine S100A4 est connue pour son implication dans la motilité de divers types cellulaires tels que les fibroblastes, les macrophages ou encore les cellules cancéreuses. En outre, S100A4 est capable d’interagir avec de nombreuses protéines cruciales pour la migration cellulaire telles que la myosine-IIA, l’actine, la tropomyosine, la rhotékine, les septines 2,6 et 7, CCN3 ou encore la transglutaminase 2.<p><p>Nous avons montré que des souris déficientes pour S100A4 ne présentent aucune modification majeure au niveau des cellules T situées dans le thymus ou en périphérie. Nous avons observé que la protéine S100A4 est principalement exprimée par les cellules T mémoires effectrices des populations de LT CD4+ ou CD8+. Cependant, la présence de la protéine ne semble pas requise pour la migration in vitro des LT mémoires. De plus, des expériences d’infections bactériennes par Listeria monocytogenes nous ont permis de démontrer que la réponse immunitaire mémoire des cellules T n’est pas affectée par l’absence de S100A4. En outre, la différenciation in vitro de cellules T CD4+ naïves en diverses sous-populations effectrices n’est pas modifiée suite à l’absence de la protéine dans les cellules. Finalement, nous avons étudié l’implication de la protéine S100A4 dans le développement de maladies immunitaires impliquant la migration de cellules T. Nos modèles d’intérêts ont été la colite et l’encéphalomyélite auto-immunitaire expérimentales. La protéine S100A4 n’est pas cruciale pour l’induction de ces deux pathologies, puisque son absence ne modifie pas leur développement.<p><p>Notre étude démontre clairement que la protéine S100A4 n’est pas requise pour la motilité des cellules T.<br>Doctorat en Sciences biomédicales et pharmaceutiques<br>info:eu-repo/semantics/nonPublished
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Basepayne, Tamara Lee. "Characterization of the zebrafish zipper interacting protein kinase homolog." Scholarly Commons, 2012. https://scholarlycommons.pacific.edu/uop_etds/817.
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The regulation and maintenance of normal cell movements and shape play a vital role in the normal development and health of every living thing. The characterization of 6 zebrafish Zipper Interacting Protein Kinase homolog has helped to better understand how changes in cell cytoskeletal elements can lead to changes in cell shape and movement. Zebrafish are ideal model organisms for studying ZIPK because it has been previously shown that zebrafish ZIPK has closer sequence homology to human ZIPK than rodent ZIPK, and because zebrafish embryos are ideal for studying cell shape and movement in vivo. Using Whole Mount In Situ Hybridization we found that the zebrafish ZIPK is expressed during all stages of embryonic development, but most importantly during gastrulation when cell motility and changes in cell shape can best be studied. To determine where zebrafish ZIPK is expressed at the sub-cellular level, GFP-ZIPK and Flag-ZIPK clones were created and used for transfecting into Hek293T cells and Hela Cells. From these transfections, cell counterstaining and confocal microscopy we found that ZIPK is expressed ubiquitously throughout the cell, although mainly cytoplasmic. To study the effects on cell shape various ZIPK mutants were created through site-directed mutagenesis. These mutants were made to study the effects of the kinase domain of the protein, or other functional domains within the protein. From these studies it was shown that ZIPK does affect cell shape through changes in the actomyosin cytoskeleton resulting in aberrant cytoskeletal structures. Finally, we have also shown through phosphorylation assays that ZIPK phosphorylates and thus regulates MYPT-1, a scaffolding protein of the myosin protein phosphate complex and directly phosphorylates myosin light chain, both of which play a role in changes in cell shape and movement.
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Hornung, Alexander. "Two-dimensional migration of human effector T-cells : integrin-dependent motility studies under shear stress." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM4051/document.
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Bien que la description qualitative et phénoménologique de la migration cellulaire soient décrites de façon minutieuse dans son approche holistique, des mécanismes de base et connus depuis longtemps n’ont pas encore été explorés quantitativement avec une approche "bottom-up". Un de ces exemples est le comportement migratoire en deux dimensions des lym- phocytes T effecteurs humains. Alors que leur comportement in vivo est déjà connu depuis longtemps et décrit qualitativement, une approche quantitative in vitro offre de nombreuses perspectives. Les interactions des intégrines LFA-1 et VLA-4 avec leurs ligands respectifs ICAM-1 et VCAM-1 ont déjà été étudiées et sont les principales molécules impliquées dans la migration des lymphocytes T effecteurs. Du fait de leur importance dans l’organisation de la mobilité, ces deux protéines sont les principaux objets d’étude de cette thèse. La majorité des travaux précédents ont été réalisés en observant les lymphocytes T dans des tissus vi- vants dont la composition et la densité des molécules d’adhésion ne peuvent ni être déterminées ni contrôlées de façon précise. Nous avons developpés des substrats artifi- ciels permettant d’imiter et de contrôler ces caractéristiques adhésives afin d’examiner et de relier les propriétés physiques des cellules tels que la vitesse ou l’index de mi- gration orientée, avec une réponse cellulaire donnée ainsi que d’associer un type de mouvement avec des interactions intégrines-ligands spécifiques. Pour aller plus loin, nous avons à nouveau analysé la conformation des intégrines puis l’avons modulé pour altérer leur affinité et changer les propriétés précédemment décrites<br>The ability of T-lymphocytes to migrate to sites of inflammation towards all different types of tissues based on the interplay between biochemical and mechanical signaling is unique among human cells and underlines the importance of their complex motility apparatus relying on multiple stimuli. A crucial part within the leukocyte adhesion cascade is the firm attachment of the immune cell to the inner wall of the blood vessel and the subsequent migration along its surface until crossing the endothelial cell barrier. These migrational steps are guided not only by the shear stress to which the cell is exposed to by the flow of blood, but also by expression of adhesion molecules, the most important among them are ICAM-1 and VCAM-1 and their integrin counterparts LFA-1 and VLA-4, expressed by the immune cell. These proteins are crucial not only in a mechanically anchoring sense, but they also play a part in an intracellular signaling process leading to a change in migrational direction, overall cell affinity and phenotype. Few is known about how all components shape the movement behaviour on a quantitative level, raising questions about hierarchy, affinity and density of the involved proteins. Besides enhancing the general knowledge of the mechanisms of T-cell migration, the role of ICAM-1 and VCAM-1 in various diseases makes this study a promising endeavour. The approach taken in this thesis is to dissect and recompose the important adhesion molecules on a laminal flow chamber to link the cell’s response to them to specific movement properties and answer the questions addressed above
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Sin, Connie. "Cellular and molecular consequences of S100A4-induced motility in rat breast tumour Rama 37 cells." Thesis, Aston University, 2013. http://publications.aston.ac.uk/27394/.
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Since the first discovery of S100 members in 1965, their expressions have been affiliated with numerous biological functions in all cells of the body. However, in the recent years, S100A4, a member of this superfamily has emerged as the central target in generating new avenue for cancer therapy as its overexpression has been correlated with cancer patients’ mortality as well as established roles as motility and metastasis promoter. As it has no catalytic activity, S100A4 has to interact with its target proteins to regulate such effects. Up to date, more than 10 S100A4 target proteins have been identified but the mechanical process regulated by S100A4 to induce motility remains vague. In this work, we demonstrated that S100A4 overexpression resulted in actin filaments disorganisation, reduction in focal adhesions, instability of filopodia as well as exhibiting polarised morphology. However, such effects were not observed in truncated versions of S100A4 possibly highlighting the importance of C terminus of S100A4 target recognition. In order to assess some of the intracellular mechanisms that may be involved in promoting migrations, different strategies were used, including active pharmaceutical agents, inhibitors and knockdown experiments. Treatment of S100A4 overexpressing cells with blebbistatin and Y-27632, non muscle myosin IIA (NMMIIA) inhibitors, as well as knockdown of NMMIIA, resulted in motility enhancement and focal adhesions reduction proposing that NMMIIA assisted S100A4 in regulating cell motility but its presence is not essential. Further work done using Cos 7 cell lines, naturally lacking NMMIIA, further demonstrated that S100A4 is capable of regulating cell motility independent of NMMIIA, possibly through poor maturation of focal adhesion. Given that all these experiments highlighted the independency of NMMIIA towards migration, a protein that has been put at the forefront of S100A4-induced motility, we aimed to gather further understanding regarding the other molecular mechanisms that may be at play for motility. Using high throughput imaging (HCI), 3 compounds were identified to be capable of inhibiting S100A4-mediated migration. Although we have yet to investigate the underlying mechanism for their effects, these compounds have been shown to target membrane proteins and the externalisation of S100 proteins, for at least one of the compounds, leading us to speculate that preventing externalisation of S100A4 could potentially regulate cell motility.
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Bailey, Kelly M. "Focal adhesion kinase mediates caveolin-1 expression during epithelial to mesenchymal transition a novel pathway regulating aspects of cell motility in cancer /." Morgantown, W. Va. : [West Virginia University Libraries], 2008. https://eidr.wvu.edu/etd/documentdata.eTD?documentid=5804.
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Thesis (Ph. D.)--West Virginia University, 2008.<br>Title from document title page. Document formatted into pages; contains x, 229 p. : ill. (some col.). Includes abstract. Includes bibliographical references.
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Paiwand, Frouz Frozan. "RHAMM, CD44 expression and erk activation are linked in malignant human breast cancer cells and are associated with cell motility." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ46047.pdf.
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Marth, Wieland. "Hydrodynamic Diffuse Interface Models for Cell Morphology and Motility." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-204651.
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In this thesis, we study mathematical models that describe the morphology of a generalized biological cell in equilibrium or under the influence of external forces. Within these models, the cell is considered as a thermodynamic system, where streaming effects in the cell bulk and the surrounding are coupled with a Helfrich-type model for the cell membrane. The governing evolution equations for the cell given in a continuum formulation are derived using an energy variation approach. Such two-phase flow problems that combine streaming effects with a free boundary problem that accounts for bending and surface tension can be described effectively by a diffuse interface approach. An advantage of the diffuse interface approach is that models for e.g. different biophysical processes can easily be combined. That makes this method suitable to describe complex phenomena such as cell motility and multi-cell dynamics. Within the first model for cell motility, we combine a biological network for GTPases with the hydrodynamic Helfrich-type model. This model allows to account for cell motility driven by membrane protrusion as a result of actin polymerization. Within the second model, we moreover extend the Helfrich-type model by an active gel theory to account for the actin filaments in the cell bulk. Caused by contractile stress within the actin-myosin solution, a spontaneous symmetry breaking event occurs that lead to cell motility. In this thesis, we further study the dynamics of multiple cells which is of wide interest since it reveals rich non-linear behavior. To apply the diffuse interface framework, we introduce several phase field variables to account for several cells that are coupled by a local interaction potential. In a first application, we study white blood cell margination, a biological phenomenon that results from the complex relation between collisions, different mechanical properties and lift forces of red blood cells and white blood cells within the vascular system. Here, it is shown that inertial effects, which can become of relevance in various parts of the cardiovascular system, lead to a decreasing tendency for margination with increasing Reynolds number. Finally, we combine the active polar gel theory and the multi-cell approach that is capable of studying collective migration of cells. This hydrodynamic approach predicts that collective migration emerges spontaneously forming coherently-moving clusters as a result of the mutual alignment of the velocity vectors during inelastic collisions. We further observe that hydrodynamics heavily influence those systems. However, a complete suppression of the onset of collective migration cannot be confirmed. Moreover, we give a brief insight how such highly coupled systems can be treated numerically using finite elements and how the numerical costs can be limited using operator splitting approaches and problem parallelization with OPENMP<br>Diese Dissertation beschäftigt sich mit mathematischen Modellen zur Beschreibung von Gleichgewichts- und dynamischen Zuständen von verallgemeinerten biologischen Zellen. Die Zellen werden dabei als thermodynamisches System aufgefasst, bei dem Strömungseffekte innerhalb und außerhalb der Zelle zusammen mit einem Helfrich-Modell für Zellmembranen kombiniert werden. Schließlich werden durch einen Energie-Variations-Ansatz die Evolutionsgleichungen für die Zelle hergeleitet. Es ergeben sie dabei Mehrphasen-Systeme, die Strömungseffekte mit einem freien Randwertproblem, das zusätzlich physikalischen Einflüssen wie Biegung und Oberflächenspannung unterliegt, vereinen. Um solche Probleme effizient zu lösen, wird in dieser Arbeit die Diffuse-Interface-Methode verwendet. Ein Vorteil dieser Methode ist, dass es sehr einfach möglich ist, Modelle, die verschiedenste Prozesse beschreiben, miteinander zu vereinen. Dies erlaubt es, komplexe biologische Phänomene, wie zum Beispiel Zellmotilität oder auch die kollektive Bewegung von Zellen, zu beschreiben. In den Modellen für Zellmotilität wird ein biologisches Netzwerk-Modell für GTPasen oder auch ein Active-Polar-Gel-Modell, das die Aktinfilamente im Inneren der Zellen als Flüssigkristall auffasst, mit dem Multi-Phasen-Modell kombiniert. Beide Modelle erlauben es, komplexe Vorgänge bei der selbst hervorgerufenen Bewegung von Zellen, wie das Vorantreiben der Zellmembran durch Aktinpolymerisierung oder auch die Kontraktionsbewegung des Zellkörpers durch kontraktile Spannungen innerhalb des Zytoskelets der Zelle, zu verstehen. Weiterhin ist die kollektive Bewegung von vielen Zellen von großem Interesse, da sich hier viele nichtlineare Phänomene zeigen. Um das Diffuse-Interface-Modell für eine Zelle auf die Beschreibung mehrerer Zellen zu übertragen, werden mehrere Phasenfelder eingeführt, die die Zellen jeweils kennzeichnen. Schließlich werden die Zellen durch ein lokales Abstoßungspotential gekoppelt. Das Modell wird angewendet, um White blood cell margination, das die Annäherung von Leukozyten an die Blutgefäßwand bezeichnet, zu verstehen. Dieser Prozess wird dabei bestimmt durch den komplexen Zusammenhang zwischen Kollisionen, den jeweiligen mechanischen Eigenschaften der Zellen, sowie deren Auftriebskraft innerhalb der Adern. Die Simulationen zeigen, dass diese Annäherung sich in bestimmten Gebieten des kardiovaskulären Systems stark vermindert, in denen die Blutströmung das Stokes-Regime verlässt. Schließlich wird das Active-Polar-Gel-Modell mit dem Modell für die kollektive Bewegung vom Zellen kombiniert. Dies macht es möglich, die kollektive Bewegung der Zellen und den Einfluss von Hydrodynamik auf diese Bewegung zu untersuchen. Es zeigt sich dabei, dass der Zustand der kollektiven gerichteten Bewegung sich spontan aus der Neuausrichtung der jeweiligen Zellen durch inelastische Kollisionen ergibt. Obwohl die Hydrodynamik einen großen Einfluss auf solche Systeme hat, deuten die Simulationen nicht daraufhin, dass Hydrodynamik die kollektive Bewegung vollständig unterdrückt. Weiterhin wird in dieser Arbeit gezeigt, wie die stark gekoppelten Systeme numerisch gelöst werden können mit Hilfe der Finiten-Elemente-Methode und wie die Effizienz der Methode gesteigert werden kann durch die Anwendung von Operator-Splitting-Techniken und Problemparallelisierung mittels OPENMP
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Challa, Anil Kumar. "Identification and functional analysis of Zebrafish orthologs of genes." Connect to this title online, 2003. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1061302731.
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Thesis (Ph. D.)--Ohio State University, 2003.<br>Document formatted into pages; contains 119 p. Includes bibliographical references. Abstract available online via OhioLINK's ETD Center; full text release delayed at author's request until 2005 Aug. 19.
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Adanja, Ivan. "Automated tracking of unmarked cells migrating in three-dimensional matrices." Doctoral thesis, Universite Libre de Bruxelles, 2012. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209703.
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The goal of this thesis is the development of a tracking algorithm for populations of unmarked cancer cells that migrate in 3D in vitro gels. The tracking algorithm is intended to be a tool for analysing the motility of large population (i.e. hundreds) of cells in the context of the anti-migratory drug development and more specifically drug screening. In oncology, cancer cell migration plays pivotal roles in the spread of cancer cells from a primary tumor site to neighboring and secondary sites, i.e. the processes of tissue invasion and metastasis. Preventing such processes represents an important therapeutic approach to cancer treatment. Providing tools able to test potential anti-migratory drugs thus constitutes currently a real need in oncology therapy. The goal of drug screening in this context aims to rapidly and efficiently test the anti-migratory effects of many experimental conditions on cancer cell populations.<p>The focus in this thesis lies in two specific aspects that are important in anti-migratory drug screening: tracking cells inside an in vitro 3D environment and doing so using unmarked cells.<br>Doctorat en Sciences de l'ingénieur<br>info:eu-repo/semantics/nonPublished
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Vuta, Ravi K. "Numerical simulation of moving boundary problem." Link to electronic thesis, 2007. http://www.wpi.edu/Pubs/ETD/Available/etd-050407-082551/.
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Zhao, Rathje Li-Sophie. "Tropomyosin in Normal and Malignant Cells and the Action of Picropodophyllin on the Microfilament and Microtubule Systems." Doctoral thesis, Stockholms universitet, Wenner-Grens institut, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-27767.
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Cell motility is a fundamental process, enabling cells to migrate, for instance during embryogenesis, tissue repair and defense. Force is generated by two protein systems, which also participate in cell proliferation, control macromolecular and organelle distribution and determine the fine structure of the cell interior. The major components of these are actin and tubulin, respectively, and they are referred to as the microfilament and the microtubule systems. This thesis focuses on tropomyosin, one of many microfilament associated proteins coupled to actin dynamics and organization and expressed in several isoform variants. Altered distribution and isoform expression of tropomyosin are signatures of malignant cells and are dealt with in the current thesis. The presence of tropomyosin isoforms in protruding lamellipodia of migrating cells is demonstrated, and a method to fractionate tropomyosin depending on its organization in an easily extractable, and a more tightly bound cytoplasmic form is presented. Analysis of the loosely associated tropomyosin fraction by gel filtration chromatography revealed that most of the tropomyosins in this fraction exist in a multimeric form. It was also observed that the distribution of tropomyosin varied between non-transformed and transformed cells with most of the isoforms enriched in the loosely bound fraction in the latter category of cells. Possibly this reflects the extensive reorganization of the microfilament system observed in cancer cells and which, depending on the context, can be normalized by introduction of certain tropomyosin isoforms. Many anti-cancer drugs target the microtubule system, inhibit cell division and promote apoptosis. Here it is shown that picropodophyllin, which has promising anticancer properties has a destabilizing effect on microtubules and via the microfilament system causes cells to detach from their substratum. Furthermore, picropodophyllin interferes with stimulation of the insulin-like growth factor receptor, which is involved in growth stimulation, differentiation and survival and whose expression is up-regulated in cancer cells.
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Patel, Sabina. "The Development of Tetracycline Dependent Pancreatic Cancer Cells and the Evaluation of CapG and Gelsolin Expression on Pancreatic Cancer Cell Motility In Vitro." Thesis, University of Liverpool, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491370.
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Precise control of the level of protein expression in cells can facilitate functional studies providing information on the role of given proteins. In this thesis, I describe the generation of tetracycline-inducible pancreatic cancer cells and the subsequent use of these in the functional characterisation of an actin capping protein, CapG. Such cells were obtained in three pancreatic cancer cell lines, Panc-I, Suit-2 and MiaPaCa-2 cells through consecutive transfections with two plasmid constructs. The first of these harboured a second-generation reverse tetracycline-controlled transactivator protein (rtTA) whilst the second, contained the gene of interest (CapG or luciferase) under the control of a tetracycline response promoter element (pTRE). Suit-2 derived tetracycline inducible clones, along with stable doxycycline-inducible hepatoma cell lines, were used to study the effect of modulating CapG expression on cell motility. Here I report that stable introduction of a pTRE2hygCapG construct into two doxycycline-inducible clones derived from Suit-2 cells, Suit-2 ptet1I and Suit-2 ptet29 clones resulted in a dose and time-dependent increase of CapG expression in response to doxycycline. Moreover, doxycycline-mediated upregulation of CapG expression led to a significant increase in the wound healing capacity of Suit-2 ptet29 cells. The expression of a related actin binding and cell motility protein, gelsolin was also determined. Immunostaining of benign (n=24 patients) and malignant (n=68 patients) pancreatic ductal cells revealed higher gelsolin expression in the malignant state (P<O.OOO 1). High nuclear gelsolin was associated with reduced patient survival (P=O.OI). RNA interference (RNAi) mediated depletion of gelsolin in Panc-I, Suit-2 and MiaPaCa-2 cells led to significantly impaired motility, as assessed by either Boyden chambers or wound healing assays. To summarise, the generation of tetracycline-inducible pancreatic cancer cell lines provided a platform for functional analysis of CapG. These cell lines will also prove useful in the future, for the study ofa wide variety of proteins. The analyses of CapG and gelsolin showed that they can modulate the motility of pancreatic and hepatoma cancer cells in vitro. This suggests a potentially important role for these proteins in cancer cell dissemination. Supplied by The British Library - 'The world's knowledge'
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Brunner, Claudia. "Origin and Spatial Distribution of Forces in Motile Cells." Doctoral thesis, Universitätsbibliothek Leipzig, 2011. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-68063.
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Die selbständige, gerichtete Bewegung von biologischen Zellen ist eine der grundlegendsten und komplexesten Erscheinungen der Natur. In höher entwickelten Lebewesen spielt die Zellbewegung eine wichtige Rolle, z.B. bei der Entwicklung des Organismus, bei der Funktion des Immunsystems aber auch bei der Metastase von Krebszellen. Die physikalischen Prozesse die dieser Fähigkeit zugrunde liegen, sind im Fokus dieser Arbeit. Um besser zu verstehen welche Prozesse im Einzelnen und in welcher Kombination den Zellen erlauben sich gerichtet fortzubewegen, wurde in der vorliegenden Arbeit ein representatives Modellsystem von motilen Zellen untersucht. Fischkeratozyten bewegen sich in vitro regelmäßig und gleichförmig, relativ schnell über die Substratfläche, und stellen aus physikalischer Sicht eine optimierte, sich selbständig bewegende Polymermaschine dar.
Um Kräfte in der Bewegungsebene der Zellen zu untersuchen, wurde in der vorliegenden Arbeit eine neuartige, auf dem Rasterkraftmikroskop (RKM) basierende Methode entwickelt. Zusätzlich wurden hochaufgelöste, mit dem Phasenkontrastmikroskop aufgenommene Bilderserien analysiert und die Geschwindigkeitsverteilung in der Zelle durch Korrelationsalgorithmen bestimmt. Die Struktur des Polymernetzwerkes wurde in mit Fluoreszenzfarbstoff markierten Zellen untersucht, und elastische Eigenschaften wurden mit rheologischen RKM-Messungen bestimmt. Traktionskraftmessungen an elastischen Substraten runden das umfassende Bild ab. Durch Veränderung der molekularen Strukturen mit verschiedenen Chemikalien, die unterschiedliche Prozesse im Gesamtsystem
stören, konnte nun ein Phasenraum der Kraftgenerierungsprozesse untersucht und unterschiedliche Effekte verschiedenen Prozessen eindeutig zugeordnet werden. Es wurde somit erstmalig experimentell bewiesen, dass die Polymerisation von Aktin die treibende Kraft am vorderen Rand der Zelle ist. Darüber hinaus wurde das Verhalten des Kraftaufbaus mit einem Model beschrieben, das Aufschluss über die Funktionsweise der darunterliegenden Aktinpolymerstrukturens gibt. Desweiteren wurde in der Mitte der Zelle, zwischen vorderem Rand und Zellkörper, erstmalig eine rückwärtsgerichtete Kraft gemessen, die wichtig ist um ein Kräftegleichgewicht zu erstellen. Ein Model das auf entropischen Kräften im Polymersystem basiert, beschreibt diese kontraktilen Kräfte und ordnet sie der Depolymerisation von Aktin zu. Die Bewegung des Zellkörpers wiederum basiert auf dem Zusammenspiel dieser beiden Mechanismen, sowie der Kontraktion von Aktin und Aktinbündeln durch molekulare Motoren. Eine umfassendes Charakterisierung über verschiedene lokale Mechanismen und ihrer Wechselwirkungen konnte somit erstellt werden, und damit das Verständnis der Kraftgenerierung zur Zellbewegung vertieft.