<div>An estimated 20 million tons of adhesives are used globally each year, and the amount is continually increasing. Glues are used in nearly every economic sector but are largely consumed by key external drivers of the industry including construction and transportation equipment to replace mechanical fasteners. Many of these applications require specific functionality, like moisture resistance, desirable mechanical properties, or low toxicity. However, specific features usually occur at the expense of adhesive strength, and there is no “one size fits all” adhesive. The search for more practical and stronger glues has contributed to the development of biomimetic adhesives. Marine mussels and other sea creatures produce biological adhesives that stick well underwater. By using nature as an inspiration for better glues, we can combine stronger bonding and additional functionality into one adhesive system. Introducing the same catechol moiety used by marine organisms into synthetic polymers has allowed us to produce adhesives stronger than commercial glues in both dry and wet environments.</div><div><br></div><div>While many of these biomimetic polymer adhesives have been prepared, few have made it to market. Here, multiple biomimetic polymer adhesives are studied and optimized for different applications to provide the next step towards commercialization. The adhesives were tailored for use on different surfaces and conditions through formulation or polymer design. Structure-function studies have showed how surface energy influences optimal adhesion with catechol-containing polymers for applications in bonding dissimilar substrates while maintaining desired mechanical properties. Multiple adhesive systems were studied in mice to assess toxicity and determine viability as potential surgical glues. Underwater formulation and application methods were also pursued to improve product development strategies for offering a competitive advantage as an underwater glue. In addition to these practical-use modifications of the adhesives, industry research and market analysis was conducted to provide insight into further applications to pursue. A cost analysis led to creating new synthetic strategies for cost-reduction and scale-up, both of which are essential in the commercialization of a catechol-containing polymer adhesive.<br></div>

<p>New acceptor moieties with extended conjugation have been developed  for further understanding of structure-property relationships in donor-acceptor type semiconducting polymers. These diketopyrrolopyrrole or isoindigo based conjugated polymers have been demonstrated as functional materials in organic field effect transistors, photoacoustic imaging and organic electrochemical transistors. With demonstrations of semiconducting molecular design, we hope to spark new research directions especially on deeper investigation of charge transport dependence on chemical structures, and new design strategies of acceptor moieties with extended conjugation could be applied for targeted applications.</p>

Acquisition of X-ray crystallographic data is always accompanied by structural degradation owing to the absorption of energy. The application of high-fluency X-ray sources to large biomolecules has increased the importance of finding ways to curtail the onset of X-ray-induced damage. A significant effort has been under way with the aim of identifying strategies for protecting protein structure. A comprehensive model is presented that has the potential to explain, both qualitatively and quantitatively, the structural changes induced in crystalline protein at 100 K. The first step is to consider the qualitative question: what are the radiation-induced intermediates and expected end products? The aim of this paper is to assist in optimizing these strategies through a fundamental understanding of radiation physics and chemistry, with additional insight provided by theoretical calculations performed on the many schemes presented.

Synaptic plasticity, in its broadest sense, can be defined as the ability of synapses to be modified structurally and functionally in response to various internal and external factors. Growing evidence has established that at the very core of these modifications are alterations in the cytoskeletal architecture. This discovery has led to the unearthing of a number of signaling pathways that might be involved in cytoskeletal regulation and also in the regulation of other aspects of synapse development and plasticity. In this regard, polarity proteins and secreted morphogens such as the Wnt proteins, typically involved in embryonic development, are emerging as critical determinants of synaptic growth and plasticity. However, their mechanism of action at synapses needs further investigation. Additionally, not much is known about how these morphogens are secreted or transported across synapses. Using the Drosophila larval NMJ as a model system, I have addressed aspects related to the issues mentioned above in the subsequent body of work. In the first half of my thesis, I have uncovered a role for the aPKC/Baz/Par-6 polarity protein complex in the regulation of the postsynaptic actin cytoskeleton in conjunction with the lipid and protein phosphatase PTEN. In the second half of my thesis, I have contributed to the elucidation of mechanisms underlying the secretion of Wg, the Drosophila Wnt homolog. Our findings suggest that Wnts might be secreted via a previously unidentified mechanism involving the release of exosome like vesicles from the presynapse and this process requires Evi/Wntless (Evi), a protein dedicated to Wnt secretion. Alterations in signaling pathways and aberrant cytoskeletal regulation lead to a variety of neurological disorders. The body of work in this thesis will provide a deeper understanding of the mechanisms involved in synaptic plasticity and provide a basis for uncovering similar pathways in the context of vertebrate synapses.

L’objectif de ces travaux est d’analyser les propriétés rhéologiques de l’acétate de cellulose, un polymère biosourcé. Afin de faciliter la mise en œuvre de l’acétate de cellulose, il est usuel d’y incorporer des plastifiants. Dans le but de développer la transformation de ce polymère par des procédés industriels conventionnels, il est nécessaire d’obtenir davantage d’informations rhéologiques pour différentes conditions d’écoulement. Le comportement rhéologique particulier d’un acétate de cellulose plastifié de degré de substitution 2,45 a été étudié à l’aide de différentes mesures rhéologiques. Des mesures viscoélastiques dans le régime linéaire ont été menées et des comportements inattendus ont été mis en évidence. Par rapport à des polymères thermoplastiques conventionnels, la structure et les dynamiques des relaxations des chaînes macromoléculaires d’acétate de cellulose semblent être plus complexes que celles des polymères synthétiques communs. Ces observations ont été confirmées par des mesures dans le régime non linéaire. Les résultats suggèrent que le comportement viscoélastique des chaînes d’acétate de cellulose n’est pas contrôlé par des enchevêtrements mais plutôt par une autre longueur de corrélation définie par l’existence de points d’interactions fortes entre les chaînes nommés stickers. Ces interactions engendrent un comportement d’échelle inhabituel suivant le taux de plastifiant et la température. / This present work deals with the rheological properties of cellulose acetate which is a biobased polymer manufactured from cellulose. In order to facilitate its forming process, cellulose acetate is usually blended with plasticizers. As the conventional industrial processes need rheological information for different flow conditions, viscoelastic behaviour of a plasticized cellulose acetate with a degree of substitution of 2,45 was investigated by various rheology experiments. Measurements in the linear regime were carried out for various plasticizer contents and some unexpected behaviours have been highlighted. Compared to conventional thermoplastic polymers, the structure and dynamics of the macromolecular chains of cellulose acetate seem to be more complex than that of common synthetic polymers. This was confirmed by measurements in the nonlinear domain. The results suggests that the viscoelastic behaviour of cellulose acetate chains is not controlled by entanglements but rather by another correlation length related to strong interactions between chains, named stickers. These interactions confer to the polymer dynamics an unusual scaling behaviour depending on plasticizer content and temperature.

Le transport intracellulaire de cargos est un processus critique au sein des cellules eucaryotes, et notamment au niveau des neurones, pour contrôler différentes fonctions dont la maturation et la transmission synaptique. La kinésine-1 est un moteur moléculaire capable de transporter différents types de cargos, comme des organelles, des vésicules ou des assemblages macromoléculaires le long des microtubules. La kinésine-1 est un hétérotétramère constitué d’un homodimère de chaînes lourdes (KHC) associé à deux chaînes légères (KLC) ; les deux chaînes, KHC et KLC étant capables de recruter des cargos. L’un des premiers cargos de la kinésine-1 à avoir été identifiés sont les protéines JIP3/4 (JNK-Interacting Protein 3/4) ; elles jouent aussi un rôle de protéines adaptatrices pour le transport d’autres cargos de la kinésine-1. La kinésine-1 recrute les protéines JIP3/4 de deux façons distinctes et indépendantes (i) via KHC et (ii) via KLC. Le recrutement de JIP3/4 par KHC et KLC est capable, via des mécanismes moléculaires distincts, d’activer la motilité de la kinésine-1 et donc de contrôler le transport intracellulaire dans lequel elle est impliquée et les fonctions associées au sein des neurones.Au cours de mon travail de thèse, j’ai contribué à caractérisé par des approches bio-informatiques, biochimiques/biophysiques et structurales, les deux modes de recrutement des protéines JIP3/4 par la kinésine-1 : (i) via KHC et (ii) via KLC. Ce travail a permis d’apporter des nouveaux éléments pour comprendre le mode de recrutement de ces protéines cargos/adaptatrices par la kinésine-1, mais aussi de mieux comprendre les mécanismes moléculaires de son activation par les protéines JIP3/4. / The intracellular transport of cargos is a crucial process on eukaryotic cells, and notably in neurons, in order to regulate different functions as cell’s maturation and synaptic transmission. The Kinesin-1 is a molecular motor capable of transporting different types of cargos as organelles, vesicles and macromolecular assemblies along the microtubules. It is a heterotetramer composed by a homodimer of heavy chains (KHC) bound to two light chains (KLC), where both KHC and KLC are capable of cargos recruitment. One of the first identified cargos of Kinesin-1 is JIP3/4 (JNK-Interacting Protein 3/4), which are also adaptor proteins, intermediating the transport of other cargos. Kinesin-1 recruits JIP3/4 by two different and independent modes, (i) via KHC and (ii) via KLC. Therefore, JIP3/4 recruitment by KHC and KLC activates the motility of Kinesin-1, by distinct mechanisms, allowing the intracellular transport of cargos and the associated functions in neurons. During my PhD, I contributed to the characterization of the dual binding mode of Kinesin-1 and JIP3/4 by bioinformatical, biochemical/biophysical and structural approaches. This work allowed a better understanding of the cargos’ recruitment by Kinesin-1, as well as the molecular mechanisms of Kinesin-1 activation by JIP3/4.

Bakterielle Exopolysaccharide (EPS) tragen bei in situ-Bildung durch die Immobilisierung von Wasser maßgeblich zur Erhöhung der Viskosität fermentierter Milchprodukte bei. Die Wirkung ist grundsätzlich mit der kommerzieller Hydrokolloide auf pflanzlicher oder Algenbasis vergleichbar, wird jedoch auf Grund der komplexen Wechselwirkungen mit der Lebensmittelmatrix noch immer kontrovers diskutiert. Ziel der Arbeit war es, nach Kultivierung ausgewählter Milchsäurebakterien EPS in entsprechenden Mengen zu isolieren, um die makromolekularen Eigenschaften zu analysieren und in Beziehung zur chemischen Struktur und Funktionalität zu setzen. Zunächst konnte die in situ-EPS-Bildung durch Batch-Kultivierungen von Milchsäurebakterien im Bioreaktor derart gesteigert werden, dass eine anschließende Isolierung verschiedener EPS-Fraktionen mit einer Reinheit von bis zu 89% (Hetero-EPS) bzw. 99% (Dextrane) möglich wurde. Dies ermöglichte die erstmalige Beschreibung oder Bestätigung der chemischen Strukturen aller ausgewählten EPS. Der Verzweigungsgrad der Dextrane war über Temperatur und pH während der mikrobiellen Synthese steuerbar. Die Einzelschritte der Isolierung wurden außerdem so angepasst, dass makromolekulare Eigenschaften der EPS wie Molekülmasse oder intrinsische Viskosität durch die Isolierung nicht beeinflusst wurden. Die umfassende Untersuchung der makromolekularen Eigenschaften der EPS in wässriger Lösung bildete die Basis für die Erklärung ihrer phänomenologischen Eigenschaften und Funktionalität in fermentierten Produkten. Es zeigte sich, dass fadenziehende EPS höhere intrinsische Viskositäten als nichtfadenziehende EPS aufwiesen. Die intrinsische Viskosität war weiterhin vom Isolierungsverfahren und damit von der Isolatreinheit unabhängig. Durch die damit verbundenen Zeit- und Kosteneinsparungen während der Isolierung eröffnet dies die Möglichkeit, mikrobielle EPS ökonomisch sinnvoll einzusetzen. Durch Scherbehandlung wässriger EPS-Lösungen wurde, unabhängig vom Schersystem, ein linearer Zusammenhang zwischen Viskosität und Molekülmasse nachgewiesen und so das Potential zur gezielten Modifizierung von EPS aufgezeigt. Kinetische Untersuchungen mit ultraschallbehandelten EPS-Lösungen ermöglichten eine Bewertung der Scherempfindlichkeit, die im Einklang mit Untersuchungen zur thermischen und chemischen Belastung von EPS stand. Zur Beurteilung der Funktionalität wurden EPS-Isolate zu rekonstituierter Magermilch vor chemischer Säuerung mit Glucono-δ-lacton zugesetzt. Die resultierende Festigkeit der Modellmilchgele korrelierte mit der absoluten EPS-Konzentration und war somit unabhängig von der Isolatreinheit. Gescherte EPS besaßen eine geringere Molekülmasse und intrinsische Viskosität, was zu geringeren Gelfestigkeiten führte. Die in der Literatur bisher wenig untersuchten kapsulären, zellgebundenen EPS konnten mittels Rasterelektronenmikroskopie visualisiert und ihr Effekt auf die Eigenschaften der Zelloberfläche analysiert werden. Die gewonnenen Erkenntnisse zeigten, dass kapsuläre EPS die Hydrophobizität der Zelloberfläche verringern sowie die Wasserbindung und Gelfestigkeit bei Zusatz zu Modellmilchgelen im Vergleich zu Zellen ohne kapsuläre EPS erhöhen.

<p dir="ltr">Water molecules present an obstacle between most synthetic adhesives and surfaces, limiting molecular contact between the glue and substrates. Water can also hydrolyze or swell bulk adhesives, weakening cohesive strength. Nature has solved these challenges for millennia. Marine mussels’ ability to adhere well to wet surfaces stems from an uncommon amino acid, 3,4-dihydroxyphenylalanine (Dopa). The amino acid Dopa contains a catechol moiety that contributes to adhesion and cohesion through hydrogen bonding, metal coordination, and oxidative cross-linking. Hence, biomimetic systems often incorporate catechol groups to provide strong adhesion in both dry and wet environments. In addition to Dopa, mussel adhesive proteins are rich in cationic amino acids lysine and arginine. Previous studies have suggested that cations could displace surface-bound ions, enhancing surface adhesion. However, adhesion performance varied between systems, with no agreement on whether cations are advantageous or disadvantageous. A clear picture of how cations influence underwater adhesion has yet to emerge; therefore, this thesis aims to systematically study these effects.</p><p dir="ltr">In Chapter 2, the synthesis of catechol-containing biomimetic polymers with varying amounts of quaternary ammoniums is presented. Quaternary ammoniums, unlike protonated primary amines, contain non-reactive cations and were used to isolate effects from only charges on adhesion. In Chapter 3, differences between reactive primary amines and quaternary ammoniums were investigated. Structure-function studies have shown how cations influence bulk cohesion versus surface adhesion in dry, under deionized water, and under salt water. The roles of cations in adhesion were complex, with both cohesive and surface bonding relevant in different ways, sometimes even working in opposite directions.</p><p dir="ltr">Furthermore, a styrene-based catechol-containing polymer with excellent underwater adhesion performance is ready to enter the market, but several barriers hinder its industrial implementation. In Chapter 4, new synthetic strategies were developed to scale up and reduce the cost of producing p[vinylcatechol-<i>co-</i>styrene], which are essential for commercialization. This was achieved by selecting cheaper starting materials, switching from anionic to suspension polymerization, and optimizing deprotection reaction conditions. This change also improved adhesion in both dry and underwater conditions. This work is presented as part of our effort to advance the design of adhesives that function in challenging environments.</p>

There is an emerging threat of Neisseria gonorrhoeae strains that are resistant to all antibiotics. Because of this, the purpose of this research is to isolate, analyze, and partially characterize a new inhibitor(s) of N. gonorrhoeae. Since there is an unknown molecule secreted by Candida albicans that inhibits N. gonorrhoeae, this molecule can be partially characterized using 1H NMR Spectroscopy to assist in the development of a new antibiotic compound. It was hypothesized that quorum-sensing molecules, trans, trans- farnesol, tyrosol, phenylethyl alcohol, and tryptophol, could be possible candidates for the inhibitor. Because of this, 1H NMR spectra for these quorum-sensing molecules were obtained to serve as controls. Column chromatography and fractionation was used to isolate the inhibitor in large scale from C. albicans grown in salts-based media. Attempts to isolate the inhibitor in large scale, however, was unsuccessful since no inhibition of N. gonorrhoeae was observed. Because of this, analysis of growth media was conducted to test the media effect on producing the inhibitor. C. albicans was grown in liquid chocolate, liquid white chocolate, salts-based, and YPD media in aerobic and candle jar environments. Analysis of growth media in different environments suggests that liquid chocolate and salts-based media retain the inhibitory activity. 1H NMR spectra were obtained for the isolated molecule in liquid chocolate and salts-based media in both aerobic and candle jar environments. Analysis of this 1H NMR suggested that the inhibitor could be isolated from either the aerobic or candle jar environment for both liquid chocolate and salt-based media because a clear peak between 3.5 and 4.0 ppm was observed in all spectra. Comparison of 1H NMR spectra from quorum-sensing molecules with spectra from the isolated molecule suggests that the inhibitor is not a quorum-sensing molecule. The peaks represented by the inhibitor cannot be fully characterized and thus, either correspond to a single molecule or a complex molecular structure. It can be concluded that the inhibitor secreted by C. albicans to inhibit N. gonorrhoeae is a new unknown compound.

No description available.