Stimuli responsive polymers (SRP) have attracted a lot of attention, due to their potential and promising applications in many fields, as protein-ligand recognition, on-off switches for modulated drug delivery or artificial organs. Poly(N-isopropylacrylamide) (PNIPAM) is one of the most widely studied polymers due to its lower critical solution temperature (LCST) at ~ 32° C in aqueous solution. Additionally, glycopolymers, where free sugar units are present, have potentially interesting applications especially in bio-recognition where sugars play an important role. In this work, our interest was focused on the synthesis of glycomonomers and its block- and random- copolymers with NIPAM. NIPAM homopolymers with an active chain transfer unit at the chain end could be prepared by RAFT. They were used as macro-chain transfer agents to prepare a variety of sugar containing responsive block copolymers from new glycomonomers by the monomer addition concept. The LCSTs of the aqueous solutions of the copolymers are affected strongly by the comonomer content, spacer chain length of the glycomonomer and the chain architecture of the copolymers. These polymers were coated on a solid substrate by spin coating and crosslinked by plasma immobilization. Characterization of the polymers was performed by nuclear magnetic resonance spectroscopy (NMR), ultraviolet (UV), dynamic light scattering (DLS, detection of aggregation behaviour) and gel permeation chromatography (GPC). Polymer films were investigated by ellipsometry, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) regarding their surface properties. Afterwards sulfation of sugar – OH groups was performed in order to obtain heparin like structure, as heparin exhibits numerous important biological activities, like good interaction with diverse proteins. Finally, affinity of the polymers (sulfated and non sulfated form) on a solid support to the endothelial cells was investigated.

Este trabalho descreve a síntese de látices poliméricos híbridos contendo a argila natural Montmorilonita (MMT) por meio da polimerização radicalar controlada via mecanismo de transferência reversível de cadeia por adição-fragmentação (RAFT) em emulsão sem adição de surfatante. Primeiramente, copolímeros anfifílicos com diferentes estruturas e composições, foram preparados por meio da polimerização via RAFT em solução e caracterizados por ressonância magnética nuclear de hidrogênio (RMN 1H) e cromatografia por exclusão de tamanho (SEC). A interação entre os copolímeros sintetizados, chamados de macroagentes RAFT, e a superfície da MMT foi estudada por meio de isotermas de adsorção experimentais, as quais foram ajustadas por modelos teóricos. Os macroagentes RAFT à base de ácido acrílico (AA), acrilato de metil éter poli(etileno glicol) (PEGA) e acrilato de n-butila (BA) apresentaram afinidade pela argila como mostraram as isotermas do \"tipo L\" (Langmuir) obtidas. Os látices híbridos preparados utilizando esses macroagentes RAFT foram analisados por microscopia eletrônica de transmissão em temperatura criogênica (cryo-TEM), que revelou lamelas de MMT decoradas com nanopartículas poliméricas. As isotermas de adsorção dos macroagentes RAFT catiônicos à base de metacrilato de 2-(dimetilamino)etila (DMAEMA), PEGA e BA foram do \"tipo H\" (alta afinidade). Esses macroagentes RAFT possibilitaram a preparação de dispersões estáveis de complexos de MMT/macroagente RAFT, o que foi verificado por espalhamento dinâmico de luz (DLS), e sua utilização na síntese de látices híbridos levou à formação de uma camada polimérica em torno das lamelas de MMT. Os filmes poliméricos nanocompósitos obtidos a partir de látices catiônicos estáveis de poli(metacrilato de metila-co-acrilato de n-butila)/MMT apresentaram melhor estabilidade térmica e melhores propriedades mecânicas do que os filmes poliméricos preparados sem adição de argila como mostraram, respectivamente, os resultados de análise termogravimétrica (TG) e de análise termodinâmico-mecânica (DMA) dos materiais. / This work describes the synthesis of hybrid polymer latexes containing natural Montmorillonite clay (MMT) by reversible addition-fragmentation chain transfer (RAFT)-mediated surfactant-free emulsion polymerization. Firstly, amphiphilic copolymers with different structures and compositions were prepared by RAFT polymerization in solution and characterized by hydrogen nuclear magnetic resonance (1H NMR) and size exclusion chromatography (SEC). The interaction between these copolymers (referred to as macroRAFT agents) and the MMT surface was studied by experimental adsorption isotherms, which were adjusted by theoretical adsorption models. MacroRAFT agents based on acrylic acid (AA), poly(ethylene glycol) methyl ether acrylate (PEGA) and n-butyl acrylate (BA) displayed affinity for MMT as shown by the \"L-type\" (Langmuir) isotherms obtained. The hybrid latexes prepared using these macroRAFT agents were analyzed by transmission electron microscopy at cryogenic temperatures (cryo-TEM), which revealed polymer-decorated MMT platelets. The adsorption isotherms of cationic macroRAFT agents based on 2-(dimethylamino)ethyl methacrylate (DMAEMA), PEGA and BA were of the \"H-type\" (high affinity). These RAFT macroRAFT agents allowed the preparation of stable dispersions of MMT/macroRAFT agents complexes, which was verified by dynamic light scattering analysis (DLS), and their use in the synthesis of hybrid latexes led to the formation of a polymer layer surrounding the MMT platelets. Nanocomposite films obtained from stable cationic latexes of poly(methyl methacrylate-co-n-butyl acrylate)/MMT showed better thermal stability and better mechanical properties than polymer films prepared without addition of clay as shown, respectively, by the results of thermogravimetric analysis (TG) and dynamic mechanical analysis (DMA) of the final materials.

Les travaux de cette thèse présentent la synthèse par une polymérisation RAFT en miniémulsion de nanoparticules fluorescentes (NPFs) polymères à coeur BODIPY copolymérisé au styrène et à couronne hydrophile biocompatible et fonctionnalisable à base de poly(oxyde d'éthylène) et de poly(acide acrylique). Les propriétés de fluorescence de ces NPFs ont été étudiées par spectroscopie de fluorescence stationnaire et résolue en temps. L'élaboration de la synthèse de ce type de NPFs, et la mise au point d'un procédé "one-pot" sont présentés dans un premier temps. Ensuite, les propriétés spectroscopiques de ces NPFs sont étudiées, notamment l'influence de la concentration en monomères de BODIPY au coeur des NPFs pouvant mener à la formation d'agrégats peu ou pas fluorescents. Les propriétés spectroscopiques (longueur d'onde d'émission de fluorescence et rendement quantique) du coeur des NPFs ont été modulées. Cela est rendu possible en réalisant la synthèse de monomères de BODIPY portant des groupements aromatiques encombrés, ou présentant différentes fonctions polymérisables. La couronne hydrophile des NPFs a également été modifiée afin d'obtenir différentes répartitions des unités acide acrylique et oxyde d'éthylène dans les chaînes de copolymères en surface. Ces nouvelles NPFs sont également synthétisées par un procédé "one-pot". Enfin, des molécules à fonctions amine (fluorophores, protéines) ont été introduites dans la couronne hydrophile de ces diverses NPFs par une chimie de couplage peptidique sur les fonctions acides carboxyliques. Des nano-senseurs de pH ratiométriques ont ainsi pu être élaborés. / This PhD work presents the synthesis of fluorescent nanoparticles (FNP) via a RAFT miniemulsion polymerisation and the analysis of their fluorescence properties. The core of the FNPs is a copolymer of styrene and a BODIPY monomer, and the shell, which is biocompatible and functionnalisable, is made of poly(ethylene oxyde) and poly(acrylic acid). First of all, the synthesis' optimisation of those FNPs is presented, and to the development of a one-pot process. Then, the fluorescence properties of those FNPs are studied, especially the impact of the BODIPY monomer concentration on the formation of non or weakly fluorescent aggregates. In order to change the FNP's spectroscopics properties (fluorescent quantum yield and emission wavelength), novel fluorescent BODIPY monomers have been synthesized. Those monomers presents either some bulky aromatics substituants, either variable polymerisable functions. The FNPS's hydrophilic shell has also been modified to get different distributions of the acrylic acid and ethylene oxyde units in the polymer chains of the FNPs' surface. Those new FNPs are also synthesized via a one-pot process. At last, molecules bearing an amine function (fluorescent dyes, proteins) have been grafted onto the differents FNPs' shell via a peptid coupling reaction on the carboxylic acid functions. As such, some pH ratiometric nano-sensors have been developped.

Polymer magnetic composite (PMC) nanoparticles have gained a large attention due to their potential use in several biomedical applications from biomedical to engineering field. Among the different heterogeneous polymerization techniques that are generally used to prepare hybrid polymer particles, miniemulsion polymerization is proved to be an efficient one. The occurrence of preferential droplet nucleation in case of miniemulsion polymerization results in a 1:1 copy of monomer droplets to the polymer particles and such a mechanistic pathway offers a suitable environment for the preparation of hybrid polymer nanoparticles in the range between 50 to 500 nm. The surfactant in miniemulsoin plays a significant role to stabilize the droplets/particles and also in the encapsulation of nanoparticles. In the present study, a new class of surfactant, called amphiphilic ionic liquid, has been employed in the field of miniemulsion. The amphiphilic ionic liquid has amazing ability to impart surface tunable characteristics to the polymer particles when present on the surface of the particles. Thus the aim of the present work is to synthesize polymer magnetic composite nanoparticles with good colloidal stability, high content of magnetic nanoparticles as well as the chance for further surface functionality. Such magnetic nanoparticles may find applications in various fields. At first, the aim of the work was to establish a suitable recipe with ionic liquid as surfactant for the execution of miniemulsion polymerization. Monodisperse polystyrene nanoparticles were possible to be synthesized reproducibly. The established recipe was utilized to carry out the synthesis of PMC nanoparticles. Iron oxide (Fe3O4) was taken as magnetic nanoparticles (MNP) and it was hydrophobized with oleic acid to disperse in styrene. The concentration of feed MNP was varied to observe its influence on the characteristics of PMC nanoparticles. Stable dispersion of magnetic polystyrene particles was possible to be synthesized up to 8 wt% feed MNP. But feeding 12 wt% MNP resulted in the development of large amount of coagulum associated with instability in the dispersion. TGA investigation confirmed a significantly lower MNP content (8.2 wt%) of the composite compared to the feed amount. TEM investigation showed inhomogeneous distribution of MNP among polystyrene particles and agglomeration of MNP was observed on the surface of polystyrene particles. Considering the inability of the single step miniemulsion polymerization for the preparation of high MNP content polymer particles, it was aimed to find a new strategy which can produce such material. Inspired from the affinity of carboxylic acid group towards the surface of MNP, it was aimed to synthesize carboxyl functionalized polystyrene which was expected to improve the interaction between polymer and magnetic nanoparticles. For this purpose, RAFT mediated miniemulsion polymerization was performed in presence of a carboxyl functionalized chain transfer agent (CTA). The colloidal stability was much better compared to the previous case of non-RAFT experiments. From a feed MNP of 8 wt%, a high final MNP content up to ~27 wt% could be achieved and all the dispersions were highly stable. The higher MNP content in the final composites compared to the feed ratio was a result of the low monomer conversion and could be adjusted by a proper tuning of AIBN to CTA mole ratio. Another significant influence of the carboxyl functionalized CTA was observed on the morphology of the composite nanoparticles. The MNP were distributed homogeneously among the PS particles. Regarding the dispersion of MNP in the individual polystyrene particles, it was observed that higher amount of CTA resulted in a homogeneous dispersion of MNP whereas higher amount of initiator ended up producing asymmetric Janus like morphology. Apart from that, due to the involvement of CTA in the polymerization, much lower molecular weight of the polystyrene chains was developed compared to the free radical process and the molecular weight distribution of PS in the composite nanoparticles became much narrower through the RAFT polymerization. Thus a relatively good control over the polymerization process was achieved through RAFT polymerization which was confirmed by a nearly linear increase of molecular weight (Mn) with time of polymerization and thus, monomer conversion. In the recipe of miniemulsion, costabilizer plays an important role to retard monomer diffusion from smaller to larger droplets. Hexadecane, being the most frequently used costabilizer for miniemulsion, has been employed in this study so far. But its volatile nature restricts its utilization in several applications. For the replacement of hexadecane, a carboxyl functionalized polystyrene is employed as a costabilizer as well as a macro CTA in miniemulsoin polymerization of styrene. For this purpose, low molecular weight carboxyl bi-functionalized polystyrene (9000 g/mole) was synthesized by thermal bulk RAFT polymerization. The carboxylated polystyrene worked successfully as a costabilizer in miniemulsion and molecular weight investigation confirmed the integration of the carboxyl functionalized macro CTA into the developing polystyrene chain via RAFT polymerization. This strategy was employed successfully to synthesize stable dispersion of PMC nanoparticles with a reasonable content of MNP in the system. A homogeneous morphology was observed regarding the distribution of MNP among the polystyrene particles. The strategy of using macro CTA as costabilizer can be utilized to synthesize various functional copolymers with control architecture without any added monomer and CTA in the system. Moreover, presence of functionality within the monomer droplets can be effective to encapsulate several nanomaterials using miniemulsion polymerization.

Thesis (MSc (Chemistry and Polymer Science))--Stellenbosch University, 2008. / The Reversible addition fragmentation chain transfer (RAFT) technique is a robust and versatile technique that enables the synthesis of polymers of controlled molecular weight and polydispersity. The application of the RAFT technique in heterogeneous aqueous media has attracted great interest in academics and industry due to it being more environmentally friendly, besides its other advantages. To date, the synthesis of well-defined high molecular weight polymers via the RAFT process under industrially relevant conditions still remains a challenge for polymer chemists. The study addresses the application of the RAFT process in heterogeneous media, namely in miniemulsion polymerization, for the synthesis of AB diblock copolymers of n-butyl methacrylate and styrene. AB diblock copolymers of high molecular weight were successfully prepared via a twostep method. In the first step, a dithiobenzoate monofunctional RAFT agent was used in bulk polymerization with the first monomer, n-butyl methacrylate. After the polymerization, the majority of the polymer chains contained the thiocarbonyl-thio RAFT agent functionality, which makes the chains potentially active for chain extension. The polymeric RAFT agent (also referred to as the starting block) obtained in the first step was chain extended in the second step, in miniemulsion, upon further addition of fresh initiator and the second monomer, styrene. The effects of the initiator/RAFT agent concentration ratio on the miniemulsion systems were investigated. The miniemulsion systems used for the high molecular weight AB diblock copolymers exhibited living features despite the high polydispersity indices. Kinetic results showed an increase in the rate of polymerization throughout the polymerization. Size exclusion chromatography (SEC) results indicated significant broadening in the molecular weight distributions and a steep increase in the polydispersity during the polymerization. It was concluded that the broad molecular weight distributions and steep increase in the polydispersity was not only related to the initiator concentration but possibly due to other factors such as inhomogeneity in the miniemulsion system and a transition in the kinetic behavior during the polymerization. Secondary particle formation emerged from kinetic data and transmission electron microscopy (TEM) results, but this were not supported by the SEC results. The effect of the use of a water-soluble initiator on the miniemulsion system was also investigated. Results indicated a similar behavioral pattern as observed in the AIBNinitiated systems, and not much improvement in terms of the molecular weight distributions and polydispersity was seen. The effect of the molecular weight of the diblock copolymers on the miniemulsion system was investigated. Poly(n-butyl methacrylate)-b-poly(styrene) diblock copolymers of lower molecular weight were synthesized via the two-step process. Kinetic results indicated a similar behavioral trend as to that of the high molecular weight diblock copolymers synthesized, however SEC chromatograms showed narrower molecular weight distributions and low polydispersity indices.

Thesis (MSc (Chemistry and Polymer Science))--University of Stellenbosch, 2009. / Thesis submitted in partial fulfilment for the degree of Master of Science (polymer science) at Stellenbosch University / ENGLISH ABSTRACT: The goal of this study was to synthesize hybrid hydrogels via a chemical crosslinking mechanism through use of chain end functional poly(N-vinyl pyrrolidone)(PVP) with various topologies. The crosslinking chemistries should be benign in nature i.e. at physiological pH ranges and at 37 °C. The degradation products should be biologically tolerable and renal clearance should be possible (< 30 000 g/mol PVP0. PVP of various topologies, controlled molar mass and quantitative chain end functionality was obtained via Reversible Addition Fragmentation chain Transfer (RAFT) mediated polymerization (PDI = 1.1- 1.4). The synthesized polymers were chain end functionalized to introduce thiol or aldehyde moieties. Thiol chain ends were obtained through post polymerization modification of xanthate functional PVP with either aminolysis or reduction. The aldehyde moiety was obtained by post polymerization modification of xanthate end functional PVP with sequential hydrolysis and thermolysis. Thiol functional four arm star PVP was reacted with acrylate difunctional poly(ethylene glycol) (DIAC PEG) crosslinker under standard Michael addition conditions. In order to obtain thioether crosslinked hydrogels from tetra functional star PVP molecules it was found that a minimum thiol functionalization of 30% and a molar ratio of acrylate:thiol of 1:1.1 is required. The Schiff base reaction was used to synthesize imine or secondary amine (after reduction) crosslinks with the lysine residues on either lysozyme or bovine serum albumin (BSA) or the primary amines of bis-(2-amino ethyl)amine). Hydrogels were obtained from aldehyde functionalized PVP molecules with a fraction of functional aldehyde chain ends of 0.88 for difunctional molecules and 0.50 for tetra functional star PVP molecules with lysozyme or BSA crosslinkers. The reaction rate was favoured by lowered pH (<6.0) and an optimum molar ratio of amine : aldehyde of 1:0.8. Hydrogels were analyzed by equilibrium swelling calculations to determine the molar mass between crosslinks and the estimated pore size. In both crosslinking systems the properties of the formed hydrogels were seen to be affected by molar ratio used and by the topology of the crosslinking agent. PVP BSA and PVP PEG hydrogels were tested for 24 h and 48 h cell viability by using H9C2 myoblast cells. A concentration range of 0.25 x 10(2) to 0.01 g/mL was studied. Cell mortality was tested by Trypan blue staining and results were verified with MTT assay. A very low cell death precentage (<37%)was observed. Cells even appeared to experience a stimulatory effect after 48 h of exposure at low concentrations of PVP PEG hydrogel treatments. The properties of the formed hydrogel could be tuned by the molar mass ratios of PVP and crosslinker. The functionality of the crosslinker directly affects the molar mass between crosslinks and thus indirectly the degradation profile. It was concluded that PVP molecules with various topologies, well-defined molar masses and chain end functionality could be obtained via RAFT mediated polymerization. Obtained polymers were successfully modified and crosslinked to obtain hydrogels with stoichiometrically tuneable properties i.e. initial swelling ratio, degradation time, molar mass between crosslinks. The hydrogels had very positive cell viability results that would definitely justify further research into these materials as “tissue-mimetic” materials. / AFRIKAANSE OPSOMMING: Die doel van die studie is om poli(N-viniel pirollidoon) (PVP) gebaseerde hibried hidrogelle te sintetiseer deur middel van kovalente kruisbindings met toepaslike kruisverbinder molekules. Die chemiese reaksies betrokke in die vorming van hierdie kovalente kruisbindings moet gematig van aard wees, by fisiologiese pH en by 37 °C plaasvind. Die degradasieprodukte van die hibried-hidrogel moet biologies verdraagsaam en ook uitskeibaar deur die endokrinologiese sisteem wees. PVP van verskillende topologieë, beheerde molêre massa en kwantitatiewe kettingendfunksionaliteit is berei deur ‘n omkeerbare addisie-fragmentasiekettingoordrag (OAFO)-beheerde polimerisasieproses (PDI = 1.1-1.4). Xantaat-kettingend-PVP is aangepas na thiol of aldehied kettingendfunksies. Thiolendfunksies is verkry deur middel van ‘n aminolisasie-reaksie. Xantaat kettingend-PVP is stapsgewys gemodifiseer deur hidroliese en verhittingstappe om die aldehied ketting-endfunksionaliteit te bekom. Thiol ketting-endfunksionele vier-armige ster-PVP is kovalent gebind aan difunksionele poly(etileen glikol) deur middel van die Michael-addisiereaksie. PVP PEG hidrogelle het slegs gevorm met vier-armige ster-PVP molekules wat oor ‘n minimum van 30 % thiol-funksionaliteit beskik het en ‘n optimale molêre massa verhouding van 1:1.1 vir ankrilaat to thiol. Die Schiff-basisreaksie is gebruik om hidrogel te sintetiseer wat met imiene of amiene (na redusering) kovalente bindings gekruisbind is. In hierdie sisteme het hidrogel slegs gevorm as die aldehied-PVP molekules oor ‘n fraksie funksionele kettingend-waarde van 0.88 vir dialdehied-PVP molekules en 0.5 vir vier armige ster-PVP molekules beskik het. Die reaksie snelheid van die Schiff-basis kovalente bindings is bevoordeel deur die pH te verlaag (≤ 6.0) en ‘n gunstige molêre massa verhouding van 1:0.8 vir die nukleofiel teen oor die akseptor molekule is waargeneem. Ewewigswel berekeninge is gebruik om die molêre massa tussen kruisbindings en die gemiddelde benaderde porieë binne die drie-dimensionele interne struktuur van die hydrogel te bepaal. Die seltoksisiteit van PVP-BSA en PVP-PEG hidrogelle is oor 24 h en 48 h in die teenwoordigheid van H9c2 mioblast-selle getoets. Die hydrogel behandelings is uitgevoer in ‘n konsentrasie reeks van 0.25 x 10(2) tot 0.01 g/mL. Selmortaliteit is getoets deur ‘n Trypan-blou verkleuringstudie. Hierdie resultate is ondersteun deur MTT sel-lewensvatbaarheidstoetse. ‘n Lae selmortaliteit (≤ 37 %) is waargeneem en, opspraakwekkend, het van die selle na 48 h verhoogde vitaliteit getoon in die teenwoordigheid van lae konsentrasies PVP-PEG hidrogelle. Dit is bevind dat hidrogel eienskappe deur stoichiometriese molêre massa verhoudings asook die keuse in die topologie van kruisverbinder beïnvloed word. Hierdie eienskappe het ‘n direkte effek op die degradasieprofiel van die gevormde hidrogel. Samevattend dus is PVP molekules met ‘n variasie van topologieë, spesifieke molêre massas en kettingfunksionalitete deur middel van OAFO-gemedieerde polimerisasies gesintetiseer. Xantaatkettingendfunksionele PVP-molekules kon suksesvol omgeskakel word na die kettingendfunksionaliteit van ons keuse om ‘n hibriedhidrogel met stoichiometries-manupileerbare eienskappe te sintetiseer. Die positiewe sel-lewensvatbaarbheidstudie resultate staaf verdere ondersoeke in hierdie PVPgebaseerde hibried hidrogelmateriaal as ‘n weefsel nabootsingsmateriaal.

Thesis advisor: Thomas C. Chiles / For ten weeks during the summer of 2005, I was a Summer Undergraduate Research Fellow in an immunology laboratory at the Mayo Clinic. My research focused on the BLyS/APRIL system and the receptor TACI on the surface of B cells. Going into my summer research, I had very little experience in immunology. Throughout the process of writing this thesis, I have sought to improve upon my knowledge of immunology, building a cohesive story that begins with basic biology and ends with the results of the summer's experiments. The first part of this thesis covers topics in general immunology, and narrow down in focus to cover the function and development of lymphocytes and B cell maturation and activation. In the second part of the thesis, the background for my research is described in more detail, and topics such as autoimmunity and cancer, lipid rafts, cell polarization, the BLyS/APRIL system for B cell survival, and TACI are covered extensively. The final portion of this thesis discusses the experimental logic, a background on materials and methods, and the results of the experiments I conducted over the summer. By reading this thesis, anyone with a background in biology should become familiar with basic subjects in immunology, advanced concepts in the study of lymphocytes, the ligands BLyS and APRIL, and the receptor TACI in B cells. / Thesis (BS) — Boston College, 2006. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: College Honors Program.

Nous décrivons dans ce travail l’élaboration de latex nanocomposites à base d’oxyde de cérium en vue d’applications dans le domaine des revêtements. Deux procédés originaux ont été développés afin de contrôler la morphologie des particules. Dans un premier temps, nous avons tiré parti de la forte densité de charges des nanoparticules d’oxyde de cérium pour stabiliser des particules de latex obtenues par polymérisation en émulsion ou en miniémulsion « de Pickering ». Dans les deux cas, la réaction est conduite en présence des particules inorganiques et d’un agent complexant à caractère acide, l’acide méthacrylique, en l’absence de tout tensioactif. Des particules de latex, décorées en surface par les nanoparticules d’oxyde de cérium ont été ainsi synthétisées. Par la suite, une stratégie qui consiste à utiliser des chaînes de polymères hydrophiles, réactivables (macro-agent RAFT) et préalablement adsorbées à la surface des nanoparticules d’oxyde de cérium a été envisagée. Ces chaînes polymères comportant à la fois des fonctions carboxyliques et un groupe trithiocarbonate terminal sont capables de stabiliser la suspension colloïdale des nanoparticules et de réamorcer la polymérisation en mode semi-continu permettant ainsi l’encapsulation de l’oxyde de cérium. Une optimisation visant à utiliser un procédé batch a également été évaluée. Quelle que soit la stratégie employée, une attention toute particulière a été portée à la stabilité colloïdale du milieu ainsi qu’à la cinétique de la réaction. La morphologie des particules composites a été caractérisée par MET et cryo-MET et reliée aux conditions de modification de surface et de polymérisation / This work describes the elaboration of nanocomposite latexes containing cerium dioxide nanoparticles for coating applications. Two original approaches have been developed to control the particle morphology. First, we took advantage of the high charge density of cerium dioxide nanoparticles to stabilize latex particles obtained via emulsion or “Pickering” miniemulsion polymerization. In both cases the reaction was conducted in the presence of the inorganic particles and methacrylic acid as a complexing agent, in the absence of any added surfactant. Armored latex particles covered with cerium dioxide nanoparticules were obtained by this method. Subsequently, another approach based on the use of living hydrophilic polymer chains (macroRAFT agents) previously adsorbed on the surface of the cerium dioxide nanoparticles was considered. These copolymers both containing carboxylic acid groups and carrying a thiocarbonylthio end group led to stable aqueous dispersion of the nanoparticles and could chain extend to form an encapsulating polymer shell under starved feed emulsion polymerization conditions. An optimization using a batch process was also evaluated. For both approaches, particular attention was paid to the colloidal stability of the medium and to the kinetics of the reaction. The morphology of the nanocomposite latex particles was characterized by TEM and cryo-TEM and correlated with the surface modification and the experimental conditions

Les rafts lipidiques sont des nanodomaines membranaires enrichis en cholestérol et en sphingolipides impliqués dans la régulation de la signalisation médiée par le TCR. Néanmoins l'existence et la fonction de ces domaines sont sujettes à controverse compte tenu des difficultés expérimentales pour les étudier in vivo. En utilisant des traitements non invasifs ciblant spécifiquement la voie de biosynthèse de ces lipides, nous avons étudié l'influence de l'organisation latérale de la membrane sur l'activation lymphocytaire T. Par des approches biophysiques, nous avons démontré au sein de lymphocytes T primaires CD4+, que les molécules TCR, CD4 et Lck sont constitutivement partitionnées dans les rafts lipidiques dont est exclue CD45. De plus, cette préorganisation moléculaire modifie les paramètres d'adhésion entre le TCR. Pour étudier le rôle de ces structures au sein de cellules individuelles, nous avons développé une nouvelle méthodologie permettant de détecter et d'analyser à haut débit et de manière automatique la réponse calcique des cellules T. Nous avons confirmé l'influence des rafts membranaires dans la signalisation TCR par les rafts lipidiques joue un rôle majeur dans l'initiation de la reconnaissance antigénique des cellules T. / Lipid rafts are membrane nanodomains enriched in chrolesterol and sphingolipids, which ahave previously been implanted in TCR signaling mechanisms. This contention, however, has beacome highly controversial due to experimental difficulties to study these membrane organizations in vivo. Using non invasive treatments that target specific lipid biosynthesis, we have studied the influence of lateral membrane organization in T lymphocyte activation. By using biophysical approaches, we have demonstrated that in murine CD4+Tcelles, TCR, CD4 and Lck are constitutively and dynamically trapped in lipid rafts, whereas CD45 is excluded. Moreover, this pre-organization impacts binding of TCR to the MHC II-peptide complex and controls the initiation of early TCR signaling. To investigate the role of these structures within individual live cells, we have developed a new high throughput methodology to monitor the calcium mobilization in T cells. We have confirmed the influence of membrane rafts in TCR signaling. Our results have thus demonstrated that pre-organization of TCR signaling protagonists by lipid rafts play a major role in the initiation of T cell antigen recognition

The use of living radical polymerization methods has shown significant potential to control grafting of polymers from inert polymeric substrates. The objective of this thesis is to create advanced substrates for use in combinatorial chemistry applications through the use of g-radiation as a radical source, and the use of RAFT, ATRP and RATRP living radical techniques to control grafting polymerization. The substrates grafted were polypropylene SynPhase lanterns from Mimotopes and are intended to be used as supports for combinatorial chemistry. ATRP was used to graft polymers to SynPhase lanterns using a technique where the lantern was functionalized by exposing the lanterns to gamma-radiation from a 60Co radiation source in the presence of carbon tetra-bromide, producing short chain polystyrene tethered bromine atoms, and also with CBr4 directly functionalizing the surface. Styrene was then grafted off these lanterns using ATRP. MMA was graft to the surface of SynPhase lanterns, using g-radiation initiated RATRP at room temperature. It was found that the addition of the thermal initiator, AIBN, successfully increased the concentration of radicals to a level where we could achieve proper control of the polymerization. RAFT was used to successfully control the grafting of styrene, acrylic acid and N,N???-dimethylacrylamide to polypropylene SynPhase Lanterns via a -initiated RAFT agent mediated free radical polymerization process using cumyl phenyldithioacetate and cumyl dithiobenzoate RAFT agents. Amphiphilic brush copolymers were produced with a novel combined RAFT and ATRP system. Polystyrene-co-poly(vinylbenzyl chloride) created using gamma-radiation and controlled with the RAFT agent PEPDA was used as a backbone. The VBC moieties were then used as initiator sites for the ATRP grafting of t-BA to give a P(t-BA) brush that was then hydrolyzed to produce a PAA brush polymer. FMOC loading tests were conducted on all these lanterns to assess their effectiveness as combinatorial chemistry supports. It was found that the loading could be controlled by adjusting the graft ratio of the lanterns and had a comparable loading to those commercially produced by Mimotopes.