Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 152-171).

Nosocomial, or hospital acquired, infections, are ubiquitous within the modern clinical setting leading to over $5 billion annually of related healthcare costs in North America. All indwelling devices are highly susceptible to bacterial colonization where physico-chemical interactions between bacteria and biomaterial surfaces have been implicated as determinant factors in the fate of the initial adhesion processes. It has been proposed that by exploiting interference strategies within this critical step of infection the ability to create 'non-infective' biomaterials may be developed. / This thesis demonstrates the effectivity of North American cranberry (Vaccinium macrocarpon) derived proanthocyanidins in preventing the adhesion of pathogenic bacteria to biomaterial surfaces. Specifically, using a model of catheter associated urinary tract infection, significant reductions in initial adhesion of uropathogenic Escherichia coli and Enterococcus faecalis to PVC and PTFE were observed. With the application of colloidal theory, a mechanism of steric interference was determined as responsible for these effects. / The evidence presented implicates PAC as a molecule of interest for the development of novel biomaterials with increased resistance to bacteria colonization.

BAI2 gehört zu den Adhesion-G-Protein-gekoppelten Rezeptoren (aGPCR). Diese bisher wenig untersuchte Klasse von ca. 30 GPCR ist charakterisiert durch eine komplexe genomische Struktur, sehr große extrazelluläre Domänen und eine Vielzahl von Splicevarianten. Bisher ist bei den meisten aGPCR, wie auch bei BAI2, wenig über ihre Signaltransduktion und Funktion bekannt. Zum Verständnis der physiologischen Relevanz und zur Suche nach dem endogenen Agonist sind Kenntnisse über Proteinstruktur, Splicevarianten und Signaltransduktion essentiell. Ziel dieser Arbeit war es, mittels verschiedener in vitro-Methoden die Proteinstruktur des BAI2 in den transmembranären und intrazellulären Domänen näher zu untersuchen, sowie die natürlichen Splicevarianten in diesem Bereich, deren evolutionäre Konservierung, Gewebespezifität und Quantität zu erfassen. Für beide gefundenen Splicevarianten, eine im dritten intrazellulären Loop (ICL3) und eine im C-Terminus, konnte eine evolutionäre Konservierung auf Aminosäure- und genomischer Organisationsebene, sowie ihre Entstehung durch Exonskipping nachgewiesen werden. Nachfolgend wurden die Splicevarianten auf mögliche Interaktionen mit intrazellulären Komponenten untersucht. In dieser Arbeit konnte gezeigt werden, dass beide ICL3-Splicevarianten natürlicherweise in einem definierten Verhältnis auftreten. Außerdem konnte gezeigt werden, dass die lange ICL3-Variante des BAI2 nicht zu einer Änderung der Membrantopologie des Rezeptors, einer Homodimerisierung über die zusätzliche Aminosäuresequenz oder zu einer Interaktion mit dem C-Terminus führt. Die Splicevariante im humanen C-Terminus des BAI2 konnte als eine variable, durch Exonskipping entstandene Calcium-unabhängige Calmodulin-Bindungsstelle identifiziert werden. Diese Arbeit belegt die Existenz mehrerer BAI2-Isoformen in vivo. Die Struktur dieser Isoformen lässt unterschiedliche Funktionalitäten vermuten. Auch wenn erste Untersuchungen zwischen den beiden ICL3-Varianten keinen Unterschied ergaben, sind diese Erkenntnisse für die weitere Analyse der Signaltransduktion und Ligandensuche bedeutend. Es ist z.B. denkbar, dass sich die beiden ICL3-Varianten in der G-Protein-Kopplung oder bei der Rekrutierung von intrazellulären Interaktionspartnern unterscheiden oder dass die Splicevariante im C-Terminus zu einer Scaffold- Funktion des Calmodulins führt und/oder die Signaltransduktion durch eine permanente Bindung des Calmodulins an einer Isoform moduliert wird.

In this work, adhesion between electrolessly deposited copper and dielectric materials for use in microelectronic devices is investigated. The microelectronics industry requires continuous advances due to ever-evolving technology and the corresponding need for higher density substrates with smaller features. At the same time, adhesion must be maintained in order to preserve package reliability and mechanical performance. In order to meet these requirements two approaches were taken: smoothing the surface of traditional epoxy dielectric materials while maintaining adhesion, and increasing adhesion on advanced dielectric materials through chemical bonding and mechanical anchoring. It was found that NH3 plasma treatments can be effective for increasing both catalyst adsorption and adhesion across a range of materials. This adhesion is achieved through increased nitrogen content on the polymer surface, specifically N=C. This nitrogen interacts with the palladium catalyst particles to form chemical anchors between the polymer surface and the electroless copper layer without the need for roughness. Chemical bonding alone, however, did not enable sufficient adhesion but needed to be supplemented with mechanical anchoring. Traditional epoxy materials were treated with a swell and etch process to roughen the surface and create mechanical anchoring. This same process was found to be ineffective when used on advanced dielectric materials. In order to create controlled roughness on these surfaces a novel method was developed that utilized blends of traditional epoxy with the advanced materials. Finally, combined treatments of surface roughening followed by plasma treatments were utilized to create optimum interfaces between traditional or advanced dielectric materials and electroless copper. In these systems adhesion was measured over 0.5 N/mm with root-mean-square surface roughness as low as 15 nm. In addition, the individual contributions of chemical bonding and mechanical anchoring were identified. The plasma treatment conditions used in these experiments contributed up to 0.25 N/mm to adhesion through purely chemical bonding with minimal roughness generation. Mechanical anchoring accounted for the remainder of adhesion, 0.2-0.8 N/mm depending on the level of roughness created on the surface. Thus, optimized surfaces with very low surface roughness and adequate adhesion were achieved by sequential combination of roughness formation and chemical modifications.

Thesis (Ph.D.). / Written for the Dept. of Biology. Title from title page of PDF (viewed 2008/02/12). Includes bibliographical references.

Thesis (Ph. D.)--School of Pharmacy and School of Dentistry. University of Missouri--Kansas City, 1998. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 1996. / Vita. Includes bibliographical references (leaves [106]-127).

Thesis (Ph. D.)--Biomedical Engineering, Georgia Institute of Technology, 2007. / Radhakrishna, Harish, Committee Member ; Zhu, Cheng, Committee Member ; LaPlaca, Michelle C., Committee Member ; Garca, Andrs J., Committee Chair ; Kowalczyk, Andrew P., Committee Member.

Thesis (Ph. D.)--University of Texas at Austin, 2007. / Vita. Includes bibliographical references.

Les cellules exerçert des forces sur la matrice extra cellulaire sur laquelle elles adhérent impliquant une boulle de régulation biomécanique. Cependant les sous-jacents de par lesquelles les cellules sentent et transmettent les forces restent encore m^echaniemes à elucider. Dans la premiére partie nous allons comment le modulations géométrique les forces de tractions et la distributions des tensions dans le cytosquelette d'actine ainsi que localisation des adhésions focales sur une cellule unique en combinant l'utilisation de la technique de micropatterning et de microscopie à traction de force. Nous avons mesuré la force de traction cellulaire sur différentes formes géométriques mocropatterns (comme un U, flieche ou H) recouvert de protéines sur des gels mous de polyacrilamide 2D dans lequl sont intégrés des nanobilles fluorescenes. Nous avons montré que la géométrie influencait la distribution des forces de tractions localement tandis que l'aire projetée des differentes formes restait conservée (pour une celule). Puis nous avons comparé la force de traction cellulaire développée quand les cellules sont sur des motif contirees circulaire 2D avec des motifs discrets en forme de micropiliers 3D de la me^me rigidité . Nous avons aussi étudie comment les forces varies en fonction de la rigidité de la matrice extracellulaire dans les deux cas précédents une mesure quantitative a été faite sur la localisation spatiale des protéines d'adhésion sur les formes circulaires et aussi sur l'organisation de l'actine. Afin d'ovoir une compréhension systématique de la distribution des forces nous nous sommes concentré sur la localisation et l'orientation des forces sur différentes géométrics de motifs (V, T, Tripod et plus). Nous avons corrélé la distribution avec celle des dibers de stesses et la localisation des adhésions focales. Ensuite nous nous sommes intéressés la distribution des centrosome en corrélation avec la forces et l'organisation d'autres eléments internes. Nous avons égolement essayé de prédire la force de traction en utilisant un modele théorique. Pour finir, nous avons developpé une novelle méthode de micropatterning fabriqué à partir de brosses de polymeres de PNIPAM qui sont thermosensibles. La fonctionalisation de surface et l'adhésion des cellules sur la surface sont aussi décrites. Nous discutons également de la dépendance en température des propriétés du PNIPAm et de l' utilisation desbrosses de polymeres comme actuateur pour induire les détachments des cellules. Nous avons aussi regardé la distribution des fibres de stress quand la cellule est cultivée sur différent types de motif thermosensible. / It has grown a great interest among biophysicists that adherent cell senses substrate stiffness and geometry by the process of mechanotransduction. Cells exert force on the extra cellular matrix on which it is subjected to adhere by active mechanism, which involves biomechanical regulatory feedback loop. It is still unclear whether biomechanical,biochemical or geometrical stimuli dominates invivo. Underlying mechanism behind the way cell senses, redistributes and transmits force still needs to elucidate. In the first part we show how geometrical modulation influences traction force and tension distribution in the actin cytoskeleton, and also localization of focal adhesion at single cell level by combining use of Micropatterning and Traction force microscopy technique. We measure cell traction force seeded on different micropattened shapes(like U,arrow and H) coated with protein on 2D soft polyacrilamide gel embedded with nano beads. We show that geometrical cue redistributes traction force locally while projected area designed for a single cell is conserved. we compare cell traction force developed when cells are on a continuous 2D circular array pattern with discrete 3D micropillar array of same stiffness. We also have investigated how forces are varied with rigidity modulation of the extra cellular matrix in both these two cases. A quantitative measurement has been done on the spatially localized adhesion proteins on the circular dots and also actin re-organization. In the sencod part to achieve more systematic understanding of force distribution we have consider more on force localization and orientation on different patterned geometry( V, T, Tripod, Plus). We correlate force distribution with stress fiber and focal adhesion localization. Finally we look into centrosome distribution in correlation with force and other internal organization. An alternate approach has been made towards the development of thermoresponsive micropattern, made of poly(N-isopropyla crylamide) brushes, grafted at high surface density. Surface functionalization and cell attachment on the surface are bescribed. We discuss temperature-dependent swelling properties of PNIPAM and the polymerbrush as a microactuator which induces cell detachment. We also have looked into stress fiber distribution when cell is cultured on different thermoresponsive pattern geometries.