Le fascinant processus par lequel les signaux mécaniques sont transformés en réactions biochimiques dans la nature est appelé mécano-transduction. Le but de ma thèse a été de mimer la Nature en élaborant de nouveaux systèmes enzymatiques mécano-transductifs, i.e des matériaux capables de moduler une catalyse enzymatique lorsqu’ils sont sollicités mécaniquement. Nous avons d’abord étudié l’effet de l’étirement sur les chaînes constitutives de films multicouches de polyélectrolytes, matrices souvent utilisées pour le développement de biomatériaux intelligents. Dans le cadre d’une nouvelle stratégie axée sur la modulation mécanique de la conformation, nous avons ensuite élaboré des matrices étirables à base de poly(éthylène glycol)s. Nous avons en particulier développé de tout nouveaux revêtements covalents appelés nanogels qui se sont avérés être déposables sur le silicone étirable et fonctionnalisables avec différentes biomacromolécules, ouvrant ainsi de nouvelles routes biomimétiques. / The fascinating process by which mechanical signals are transformed into biochemical reactions in Nature is called mechanotransduction. The goal of my PhD was to mimic Nature by elaborating new types of mechanocatalytic materials, i.e materials able to modulate a catalytic activity when mechanically stimulated. We first aimed at understanding the impact of stretching on the structural properties of polyelectrolyte multilayers films, polymeric matrices often used for the design of smart biomaterials. Within the framework of a new strategy essentially relying on mechanically induced conformational changes, we then developed stretchable polymeric matrices based on poly(ethylene glycol)s. We more particularly designed new types of covalent coatings, called nanogels. We showed that these architectures were buildable on stretchable silicone and that they could be functionalized with different types of biomacromolecules; thus opening new biomimetic routes.

No description available.

Adhesive processes in aqueous media play a crucial role in nature and are important for many technological processes. However, direct quantification of adhesion still requires expensive instrumentation while their sample throughput is rather small. Here we present a fast, and easily applicable method on quantifying adhesion energy in water based on interferometric measurement of polymer microgel contact areas with functionalized glass slides and evaluation via the Johnson–Kendall–Roberts (JKR) model. The advantage of the method is that the microgel matrix can be easily adapted to reconstruct various biological or technological adhesion processes. Here we study the suitability of the new adhesion method with two relevant examples: (1) antibody detection and (2) soil release polymers. The measurement of adhesion energy provides direct insights on the presence of antibodies showing that the method can be generally used for biomolecule detection. As a relevant example of adhesion in technology, the antiadhesive properties of soil release polymers used in today’s laundry products are investigated. Here the measurement of adhesion energy provides direct insights into the relation between polymer composition and soil release activity. Overall, the work shows that polymer hydrogel particles can be used as versatile adhesion sensors to investigate a broad range of adhesion processes in aqueous media.

Throughout the study of polymeric Langmuir monolayers at the air/water (A/W) interface, the Wilhelmy plate and Langmuir-Blodgett (LB) techniques along with Brewster angle microscopy (BAM) have been identified as key methods for acquiring structural, thermodynamic, rheological and morphological information. These techniques along with surface light scattering (SLS), a method for probing a monolayer's dynamic dilational rheological properties, will be used to characterize homopolymers, poly(ethylene oxide) (PEO) and poly(ethylene glycol) (PEG), and a new class of novel polymeric surfactants, telechelic (POSS-PEG-POSS) and hemi-telechelic (POSS-PEG) polyhedral oligomeric silsesquioxane (POSS) derivatives of PEG. PEO with number average molar mass, Mn > ~ 18 kg·mol-1 form stable spread Langmuir films at the A/W interface, while oligomeric PEG have ï -A isotherms that deviate from high molar mass PEO. Nonetheless, SLS reveals that the dynamic dilational viscoelastic properties of any Mn PEG(PEO) only depend on ï and not Mn. Likewise, POSS-PEG-POSS telechelics exhibit molar mass dependent ï -A isotherms, where low ï regimes (ï < 1 mN·m-1) have PEG-like behavior, but high ï regimes were dominated by POSS-POSS interactions. SLS studies reveal that the dynamic dilational moduli of POSS-PEG-POSS are greater than either PEO or an analogous POSS compound, trisilanolcyclohexyl-POSS. The ability to control rheological properties and the hydrophilic-lipophilic balance even allows one POSS-PEG-POSS (PEG Mn = 1 kg·mol-1) to form Y-type LB-multilayer films. For POSS-PEG systems, comparisons at comparable POSS:PEG ratios reveal short PEG chains (PEG Mn ~ 0.5 kg·mol-1) yield similar viscoelastic properties as POSS-PEG-POSS (PEG Mn ~ 1 kg·mol-1), while longer PEG chains (PEG Mn ~ 2 kg·mol-1) yield lower modulus films than comparable POSS-PEG-POSS. These differences are attributed to brush-like PEG conformations in short POSS-PEG versus mushroom-like PEG conformations in long POSS-PEG at the A/W interface. These results provide insight for designing PEG-based amphiphilic nanoparticles with controlled interfacial rheology. / Ph. D.

Les nanotechnologies appliquées aux sciences pharmaceutiques ont pour but d’améliorer l’administration de molécules actives par l’intermédiaire de transporteurs nanométriques. Parmi les différents types de véhicules proposés pour atteindre ce but, on retrouve les nanoparticules polymériques (NP) constituées de copolymères “en bloc”. Ces copolymères permettent à la fois l’encapsulation de molécules actives et confèrent à la particule certaines propriétés de surface (dont l’hydrophilicité) nécessaires à ses interactions avec les milieux biologiques. L’architecture retenue pour ces copolymères est une structure constituée le plus fréquemment de blocs hydrophiles de poly(éthylène glycol) (PEG) associés de façon linéaire à des blocs hydrophobes de type polyesters. Le PEG est le polymère de choix pour conférer une couronne hydrophile aux NPs et son l’efficacité est directement liée à son organisation et sa densité de surface. Néanmoins, malgré les succès limités en clinique de ces copolymères linéaires, peu de travaux se sont attardés à explorer les effets sur la structure des NPs d’architectures alternatives, tels que les copolymères en peigne ou en brosse. Durant ce travail, plusieurs stratégies ont été mises au point pour la synthèse de copolymères en peigne, possédant un squelette polymérique polyesters-co-éther et des chaines de PEG liées sur les groupes pendants disponibles (groupement hydroxyle ou alcyne). Dans la première partie de ce travail, des réactions d’estérification par acylation et de couplage sur des groupes pendants alcool ont permis le greffage de chaîne de PEG. Cette méthode génère des copolymères en peigne (PEG-g-PLA) possédant de 5 à 50% en poids de PEG, en faisant varier le nombre de chaînes branchées sur un squelette de poly(lactique) (PLA). Les propriétés structurales des NPs produites ont été étudiées par DLS, mesure de charge et MET. Une transition critique se situant autour de 15% de PEG (poids/poids) est observée avec un changement de morphologie, d’une particule solide à une particule molle (“nanoagrégat polymére”). La méthode de greffage ainsi que l’addition probable de chaine de PEG en bout de chaîne principale semblent également avoir un rôle dans les changements observés. L’organisation des chaînes de PEG-g-PLA à la surface a été étudiée par RMN et XPS, méthodes permettant de quantifier la densité de surface en chaînes de PEG. Ainsi deux propriétés clés que sont la résistance à l’agrégation en conditions saline ainsi que la résistance à la liaison aux protéines (étudiée par isothermes d’adsorption et microcalorimétrie) ont été reliées à la densité de surface de PEG et à l’architecture des polymères. Dans une seconde partie de ce travail, le greffage des chaînes de PEG a été réalisé de façon directe par cyclo-adition catalysée par le cuivre de mPEG-N3 sur les groupes pendants alcyne. Cette nouvelle stratégie a été pensée dans le but de comprendre la contribution possible des chaines de PEG greffées à l’extrémité de la chaine de PLA. Cette librairie de PEG-g-PLA, en plus d’être composée de PEG-g-PLA avec différentes densités de greffage, comporte des PEG-g-PLA avec des PEG de différent poids moléculaire (750, 2000 et 5000). Les chaines de PEG sont seulement greffées sur les groupes pendants. Les NPs ont été produites par différentes méthodes de nanoprécipitation, incluant la nanoprécipitation « flash » et une méthode en microfluidique. Plusieurs variables de formulation telles que la concentration du polymère et la vitesse de mélange ont été étudiées afin d’observer leur effet sur les caractéristiques structurales et de surface des NPs. Les tailles et les potentiels de charges sont peu affectés par le contenu en PEG (% poids/poids) et la longueur des chaînes de PEG. Les images de MET montrent des objets sphériques solides et l'on n’observe pas d’objets de type agrégat polymériques, malgré des contenus en PEG comparable à la première bibliothèque de polymère. Une explication possible est l’absence sur ces copolymères en peigne de chaine de PEG greffée en bout de la chaîne principale. Comme attendu, les tailles diminuent avec la concentration du polymère dans la phase organique et avec la diminution du temps de mélange des deux phases, pour les différentes méthodes de préparation. Finalement, la densité de surface des chaînes de PEG a été quantifiée par RMN du proton et XPS et ne dépendent pas de la méthode de préparation. Dans la troisième partie de ce travail, nous avons étudié le rôle de l’architecture du polymère sur les propriétés d’encapsulation et de libération de la curcumine. La curcumine a été choisie comme modèle dans le but de développer une plateforme de livraison de molécules actives pour traiter les maladies du système nerveux central impliquant le stress oxydatif. Les NPs chargées en curcumine, montrent la même transition de taille et de morphologie lorsque le contenu en PEG dépasse 15% (poids/poids). Le taux de chargement en molécule active, l’efficacité de changement et les cinétiques de libérations ainsi que les coefficients de diffusion de la curcumine montrent une dépendance à l’architecture des polymères. Les NPs ne présentent pas de toxicité et n’induisent pas de stress oxydatif lorsque testés in vitro sur une lignée cellulaire neuronale. En revanche, les NPs chargées en curcumine préviennent le stress oxydatif induit dans ces cellules neuronales. La magnitude de cet effet est reliée à l’architecture du polymère et à l’organisation de la NP. En résumé, ce travail a permis de mettre en évidence quelques propriétés intéressantes des copolymères en peigne et la relation intime entre l’architecture des polymères et les propriétés physico-chimiques des NPs. De plus les résultats obtenus permettent de proposer de nouvelles approches pour le design des nanotransporteurs polymériques de molécules actives. / The goal set to nanotechnologies applied to pharmaceutical sciences is to improve drug delivery and benefits with the help of nanometer-sized vehicles. At this time different types of drug carriers had been proposed. Amongst them, block copolymer nanoparticles (NP) have been designed to allow, at the same time, efficient drug encapsulation and provide surface properties (hydrophilic layer) to the NP which are necessary for its interactions with biological systems by preventing the opsonisation and the subsequent recognition by the mononuclear macrophage system (MPS) and the rapid elimination of the drug carrier. The most prominent polymer architecture in drug delivery application is the linear di-block copolymer architecture, such as poly(ethylene glycol) blocks (PEG) linked to a polyester hydrophobic chain. PEG is the gold standard to add a hydrophilic corona to drug carrier’s surface, but its efficacy is directly linked to its surface organization and surface densities. In spite of limited success of diblock at the clinical stage, few studies have been devoted to other type of architecture such as comb-like copolymers, either for the exploration of new synthesis routes or for the characterization of particles prepared from alternative architecture polymers. We attempted in preamble of this work to define more closely the conceptual and technical framework allowing quantitative determination of PEG surface densities. This review work has been used in the experimental work to define the characterization methods. Several synthesis strategies have been developed for the preparation of comb copolymers in this work. All strategies are based on random copolymerization of dilactide with small epoxy molecules with a pendant group suitable for subsequent PEG grafting, yielding a polyester-co-ether backbone. In a second step, PEG chains have been grafted on available pendant groups (alcohol groups or alkyne) to produce the final comb copolymers. In the first part of the experimental work, esterification reaction by acylation and coupling (the Steglish reaction) allowed the preparation of a first comb-like copolymer library with PEG content varying from 5 to 50 % (w/w). The number of PEG chains (PEG grafting density) was varying while the lengths of the PEG chains and the hydrophobic PLA backbone were kept constant. The library of comb-like polymers was used to prepare nanocarriers with dense PEG brushes at their surface, stability in suspension, and resistance to protein adsorption. The structural properties of nanoparticles (NPs) produced from these polymers by a surfactant-free method were assessed by DLS, zeta potential, and TEM and were found to be controlled by the amount of PEG present in the polymers. A critical transition from a solid NP structure to a soft particle with either a “micelle-like” or “polymer nano-aggregate” structure was observed when the PEG content was between 15 to 25% w/w. This structural transition was found to have a profound impact on the size of the NPs, their surface charge, their stability in suspension in presence of salts as well as on the binding of proteins to the surface of the NPs. The arrangement of the PEG-g-PLA chains at the surface of the NPs was investigated by 1H NMR and X-ray photoelectron spectroscopy (XPS). NMR results confirmed that the PEG chains were mostly segregated at the NP surface. Moreover, XPS and NMR allowed the quantification of the PEG chain coverage density at the surface of the solid NPs. Concordance of the results between the two methods was found to be remarkable. Physical-chemical properties of the NPs such as resistance to aggregation in saline environment as well as anti-fouling efficacy, assessed by isothermal titration calorimetry (ITC), were related to the PEG surface density and ultimately to polymer architecture. In the second part of this work, grafting of PEG chains on a polyester-co-ether backbone was directly performed using cyclo-addition of PEG azide on pendant alkyne groups. The new strategy was designed to understand the contribution of PEG chains grafted on PLA backbone ends. The new polymer library was composed of PEG-g-PLA with different PEG grafting densities and PEG molecular weights (750, 2000 and 5000 D). PEG chain grafting could only take place on pendant groups with this approach. NPs were produced by different methods of nanoprecipitation, including “flash nanoprecipitation” and microfluidic technology. Some formulation variables such as polymer concentration and speed of mixing were studied in order to observe their effects on NP surface characteristics. Unlike for the first copolymer library, here the NPs size and zeta potential were found to not be much affected by the PEG content (% w/w in polymer). Sizes were also not affected by the PEG chains length. TEM images show round shaped object and as expected sizes were found to decrease with polymer concentration in the organic phase and with a decrease in mixing time of the two phases (for flash nanoprecipitation and microfluidic technology). PEG chain surface densities were assessed by quantitative 1H NMR and XPS. In the third experimental part, we explored the role of polymer architecture on drug encapsulation and release of curcumin from NPs. Curcumin has been chosen as a model with a view to develop a delivery platform to treat diseases involving oxidative stress affecting the CNS. As previously observed with blank NPs, a sharp decrease in curcumin-loaded NP size and morphology change occurred between 15 to 20 % w/w of PEG. Drug loading, Drug loading efficiency and the diffusion coefficients of curcumin in NPs are showing a dependence over the polymer architecture. NPs did not present any significant toxicity when tested in vitro on a neuronal cell line. Moreover, the ability of NPs carrying curcumin to prevent oxidative stress was evidenced and linked to polymer architecture and NPs organization. In a nutshell, our study showed the intimate relationship between the polymer architecture and the biophysical properties of the resulting NPs and sheds light on new approaches to design efficient NP-based drug carriers. The results obtained lead us to propose PEG-g-PLA comb architecture copolymers for nanomedecine development as an alternative to the predominant polyester-PEG diblock polymers.

La conception de nanoparticules (NPs) polymériques pour le transport de médicaments dans la peau repose sur la compréhension du rôle de leurs compositions chimiques sur leurs interactions avec la peau, notamment la peau pathologique. Ce travail s'est attaché à définir le rôle de la composante hydrophile des NPs sur l'administration cutanée d'un principe actif lipophile modèle (cholécalciférol). Il a été remarqué que la composition hydrophile de polymères amphiphiles à base de PLA conditionnait les propriétés physicochimiques des NPs, notamment la taille, la surface, et la structure, tout comme la protection du cholécalciférol. Concernant l'absorption cutanée sur peau intacte, la composante hydrophile de NPs de 100 nm a eu peu d'influence. Une absorption cutanée du cholécalciférol légèrement plus importante a toutefois été obtenue à partir des NPs très riches en PEG hydrophile en comparaison aux NPs peu PEGylées. A l'inverse sur peau lésée, les NPs hydrophobes et négativement chargées de PLA seul ont permis la meilleure absorption du cholécalciférol. D'une part, la dynamique de la structure des NPs très PEGylées a permis une meilleure mouillabilité de la peau et une possible extraction de lipides cutanés, pouvant faciliter l'absorption sur peau intacte. D'autre part, la composition de la peau a conditionné la structure des NPs, puisque, sur peau lésée, les espèces ioniques libérées de la peau ont déstabilisé les NPs peu ou non PEGylées. Par adhésion à la surface de la peau, les agrégats de PLA ont pu ainsi faciliter l'absorption sur peau lésée.Lors du développement de formulations de NPs, leur composition chimique est donc à optimiser selon l'état pathologique de la peau / The design of clinically efficient polymeric nanoparticles (NPs) for skin drug delivery is based on the understanding of the influence of NPs chemical composition on their interactions with the skin tissue, notably the pathological skin. The aim of this work was to determine the influence of the hydrophilic component of polymeric NPs on the delivery of a lipophilic model drug (cholecalciferol).It was noticed that the polymeric hydrophilic composition of amphiphilic PLA-based NPs conditioned the NPs physico-chemical properties, notably in terms of size, surface properties, structure and drug protection. With regard to absorption into intact skin, the hydrophilic composition of 100 nm NPs had little impact. Only a slightly greater skin absorption was obtained from NPs with high hydrophilic PEG content compared to weakly PEGylated NPs. On the contrary in impaired skin, hydrophobic and negatively charged non-PEGylated NPs (PLA NPs) provided the best drug absorption. On the one hand, the dynamic structure of highly PEGylated NPs providing better skin wettability and potential skin lipids extraction may have contributed for increased absorption in intact skin. On the other hand, skin condition altered the NPs structure since it was observed that a non-negligible quantity of ionic species was released from impaired skin, triggering the destabilization of weakly or non-PEGylated charged NPs. However, only PLA aggregates sedimented/adhered onto the skin surface, which could have facilitated absorption in impaired skin. The polymeric hydrophilic composition of NPs and the pathological skin condition are therefore essential points to consider when designing nanoformulations

A viscosimetria é um procedimento experimental simples e pouco oneroso, que pode fornecer informações valiosas sobre o volume hidrodinâmico e a conformação de macromoléculas em solução, num determinado solvente, em uma dada temperatura. Os parâmetros viscosimétricos podem ser matematicamente calculados por extrapolação gráfica, cuja execução experimental é mais demorada. Em contrapartida, é possível que a determinação seja feita por um único ponto. Neste trabalho, os dois métodos de cálculo, empregando uma série de seis equações: Huggins, Kraemer e Schulz-Blaschke, por extrapolação gráfica, e Schulz-Blaschke, Solomon-Ciuta e Deb-Chanterjee por um único ponto, foram utilizados em soluções de poli(glicol propilênico) (PPG) e copolímeros em bloco à base de poli(glicol propilênico) e poli(glicol etilênico) (EG-b-PG), com diferentes teores de poli(glicol etilênico), tendo isopropanol, tetra-hidrofurano (THF) e tolueno como solventes puros, além das misturas em proporções iguais de THF/ isopropanol e THF/ tolueno, a 25C. Os valores de viscosidade intrínseca e de algumas constantes indicaram que os solventes puros e as misturas se apresentaram no limite entre o bom e o mau solvente. Verificou-se também que o método de cálculo por um único ponto foi válido, especialmente quando a equação de Schulz-Blaschke foi empregada, apresentando um baixo percentual de erro sendo possível assim reduzir o tempo de análise para a maioria dos sistemas estudados / The viscosimetry is a simple and inexpensive polymer characterization method that provides valuable information about the hydrodynamic volume and conformation of macromolecules in solution, in a solvent, at a given temperature. The viscosimetric parameters can be mathematically calculated by graphic extrapolation. Nevertheless, these experimental tests demands a lot of time. However, it is possible to achieve results by a single point determination. In this work, the two calculation methods, employing a series of six equations: Huggins, Kraemer and Schulz-Blaschke, by graphic extrapolation; and Schulz-Blaschke, Solomon-Ciuta and Deb-Chanterjee, by a single point determination, were performed in solutions of poly(propylene glycol) (PPG) and block copolymers based on poly(glycol ethylene) and poly(glycol propylene) (EG-b-PG) with different poly (glycol ethylene) segments content. Isopropanol, tetrahydrofuran (THF) and toluene were employed as solvents. Mixtures of equal proportions of THF/ isopropanol and THF/ toluene were utilized as well. The viscosimetric determinations were performed at 25 0,1 C. The values of intrinsic viscosity and of some constants indicated that the pure solvents and the mixtures were in the limit between good and bad solvent. It was also observed that the method of calculation by a single point was valid, specially when Schulz-Blaschke equation was used, showing a low error percentage for most systems studied, reducing the time of analysis

Made available in DSpace on 2014-12-17T15:41:57Z (GMT). No. of bitstreams: 1 RobertaPMM_DISSERT.pdf: 3172444 bytes, checksum: 159d519d0473cdce848696ecb3f8e8f6 (MD5) Previous issue date: 2011-02-24 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Hybrid systems formed from polymers and transition metals have now their physical and chemical properties extensively investigated for use in electronic devices. In this work, Titanium Dioxide (TiO2) from the precursor of titanium tetrabutoxide and the composite system Poly(Ethylene Glycol)-Titanium Dioxide (TiO2-PEG) were synthesized by sol-gel method. The PEG as acquired and TiO2 and composites powders were analyzed by X-Ray Diffraction (XRD), Spectroscopy in the Infrared region with Fourier transform (IRFT), Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM) and Electrochemical Impedance Spectroscopy (EIS). In the XRD analysis were observed in the TiO2 crystal faces of one of its polymorphs - anatase phase, crystal planes in Poly (Ethylene Glycol) with considerable intensity and in the composite systems the mixture of crystal faces of their precursors isolated and reduction of crystallinity. The TG / DTG suggested increasing the thermal instability of PEG in the composite powders as TiO2 is incorporated into the system. Spectral analysis presented in the infrared overlapping bands for the polymer and metal oxide, reducing the intensity of symmetric stretching of ligand groups in the main chain polymer and angular deformations; were observed using SEM micrographs of the morphological changes suffered by composite systems with the variation of the oxide concentration. Analyses by impedance spectroscopy indicated that the increased conductivity in composite occurs in line with the addition of the metal oxide concentration in the composite system / Sistemas h?bridos formados a partir de pol?meros e metais de transi??o atualmente t?m suas propriedades f?sicas e qu?micas extensivamente investigadas para aplica??o em dispositivos eletr?nicos. Neste trabalho, o Di?xido de Tit?nio (TiO2) a partir do precursor Tetrabut?xido de Tit?nio e o sistema comp?sito Poli (Etileno Glicol)-Di?xido de Tit?nio (PEG-TiO2) foram sintetizados pelo m?todo sol-gel. O PEG como adquirido e os p?s de TiO2 e comp?sitos obtidos foram analisados por Difra??o de Raios X (DRX), Espectroscopia de Absor??o na regi?o do Infravermelho com Transformada de Fourier (EIV-TF), An?lise Termogravim?trica (TG), Microscopia Eletr?nica de Varredura (MEV) e Espectroscopia de Imped?ncia Eletroqu?mica (EIE). Nas an?lises por DRX foram observadas no TiO2, faces cristalinas de um de seus polimorfos fase anat?sio, planos cristalinos no PEG com intensidade substancial e nos sistemas comp?sitos a mistura de faces cristalinas dos seus precursores na forma isolada, bem como, redu??o da cristalinidade. As curvas TG/DTG sugeriram o aumento da instabilidade t?rmica do PEG nos p?s comp?sitos ? medida que TiO2 ? incorporado ao sistema. A an?lise espectral na regi?o do infravermelho apresentou sobreposi??o de bandas relativas ao pol?mero e ao ?xido met?lico, redu??o da intensidade de estiramentos sim?tricos dos grupos ligantes da cadeia principal polim?rica e deforma??es angulares; foram observadas atrav?s das micrografias de MEV modifica??es morfol?gicas sofridas pelos sistemas comp?sitos com a varia??o da concentra??o do ?xido. As an?lises por imped?ncia eletroqu?mica indicaram que o aumento da condutividade nos comp?sitos ocorre em conson?ncia com a adi??o da concentra??o do ?xido met?lico no sistema comp?sito

L'objectif de ce travail était d'étudier l'influence qu'exerce la microstructure des caséines sur la diffusion moléculaire de petites sondes ayant des tailles et des déformabilités différentes. La mobilité de sondes moléculaires flexibles (''PEGs'') et rigides (dendrimères) de taille variée a été étudiée dans des suspensions et des gels de PPCN et de CaNa à différentes concentrations en protéines. Les mesures ont été réalisées par RMN qui permet de sonder des mobilités translationnelles sur une distance de 1,5 µm, mais également des mobilités locales à l'échelle moléculaire (quelques nanomètres) à travers les temps de relaxation T2. Un modèle cohérent a été utilisé et un mécanisme unique a été proposé pour décrire la diffusion de petites sondes dans les deux systèmes de caséine. C'est la combinaison de différents facteurs qui doivent être pris en considération : le rapport de la taille de la sonde à la distance entre les particules obstruantes ou les points d'enchevêtrement ainsi que la flexibilité de la sonde. La mobilité locale des sondes était beaucoup moins réduite que la mobilité translationnelle dans les deux systèmes de caséine. Différents comportements de relaxation ont été obtenus entre les deux systèmes de caséine et une diminution des T2 a été mesurée dans les gels. Ces résultats ont été liés à la mobilité intrinsèque de la matrice. L'ensemble des résultats obtenus ont permis d'avoir une meilleure compréhension de la mobilité des sondes dans les systèmes caséiques et de proposer un nouveau modèle qui contredit celui déjà proposé par Le Feunteun et al. pour expliquer la diffusion des sondes dans ces systèmes. / The aim of this study was to investigate the impact of the casein microstructure on the molecular diffusion of probes with different sizes and deformabilities. The mobility of molecular flexible (‘PEG’) and rigid (dendrimer) probes of various sizes was studied in suspensions and gels of NPC and SC at various protein concentrations. Measurements were carried out by NMR, which makes it possible to probe translational mobilities over a distance of 1.5 microns, as well as local mobilities at the molecular scale (several nanometers) through the relaxation times, T2. A coherent model was used and the same mechanism was proposed to describe the diffusion of small probes in both casein dispersions. It is the combination of different factors that should be considered: the ratio of the probe size to the distance between the obstructing particles or the entanglement points, as well as the flexibility of the probe. The rotational diffusion of PEG and dendrimer probes was less hindered than translational diffusion in both casein systems. Different relaxation behaviors were observed between the two casein systems and retardation in T2 relaxation times was highlighted in rennet and acid casein gels. These results are probably related to the local mobility of the matrix. The overall results of this project led to a better understanding of probe mobility in casein systems and made it possible to propose a new model that challenges the previous one proposed by Le Feunteun et al. to describe the diffusion of probes in casein systems.

<p>The thesis describes the synthesis of chromatographic media using several different approaches, their characterizations and applications in liquid chromatography. The steps to achieve a separation column for a specific analyte are presented. The main focus of the study was the design of novel molecularly imprinted polymers.</p><p>Attachment of monolithic polymeric substrates to the walls of fused silica capillaries was studied in Paper I. With a broad literature survey, a set of common methods were tested by four techniques and ranked by their ability to improve anchoring of polymers. The best procedure was thus used for all further studies.</p><p>Synthesis of monoliths in capillary columns was studied in Paper II. With the goal of separating proteins without denaturation, various monoliths were polymerized in situ using a set of common monomers and cross-linkers mixed with poly(ethylene glycol) as porogen. The resulting network was expected to present “protein-friendly pores”. Chemometrics were used to find and describe a set of co-porogens added to the polymerization cocktails in order to get good porosity and flow-through properties.</p><p>Assessment of the macroporous structure of a monolith was described in Paper III. An alternative method to mercury intrusion porosimetry was proposed. The capillaries were embedded in a stained resin and observed under transmission electron microscope. Images were then computed to determine the pore sizes.</p><p>Synthesis of molecularly imprinted polymers grafted to a core mono-lith in a capillary was described in Paper IV. The resulting material, imprinted with local anaesthetics, was tested for its chromatographic performance. Similar imprinted polymers were characterized by microcalorimetry in Paper V. Finally, imprinted monoliths were also synthesized in a glass tube and further introduced in a NMR rotor to describe the interactions between stationary phase and template in Paper VI.</p>