INTRODUCTION : Le test de la membrane chorio-allantoïque (CAM) joue un rôle clé dans la recherche contre le cancer, permettant d'évaluer l'efficacité de nouveaux médicaments sur des cellules cancéreuses humaines greffées sur la CAM afin d'en observer les impacts sur la croissance tumorale. Malgré son importance, ce test présente cependant des limites, comme une prolifération cellulaire rapide et une compatibilité restreinte avec certaines lignées cellulaires. Notre recherche a exploré l'utilisation d'hydrogels pour le moulage ou l'impression 3D d'implants cellulaires, en combinaison avec l'essai CAM, visant à délivrer des facteurs de croissance endothéliale vasculaire (VEGF) et à favoriser la croissance de masses de cellules cancéreuses importantes. MÉTHODOLOGIE : Un hydrogel enrichi d'alginate de sodium, d'acide hyaluronique, pré-réticulé avec des ions Ca$^{2+}$, Matrigel®, VEGF, et du collagène de type I a été développé. Ses propriétés rhéologiques, physico-chimiques, et de biocompatibilité ont été évaluées, puis il a été mélangé avec des cellules cancéreuses HT1080 ou HT29, appliqué sur le CAM, et incubé à 37 ºC pour 7 jours. Les tumeurs vascularisées formées ont été analysées, quantifiant la vascularisation par VEGF via la microscopie optique et l'examen histologique. RÉSULTATS ET DISCUSSION : les résultats ont montré une viabilité cellulaire supérieure à 95% après deux jours d'incubation. Les hydrogels contenant VEGF ont induit une angiogenèse significative. Cependant, le poids des masses tumorales vascularisées a de manière inattendues diminué, suggérant une intégration limitée des hydrogels dans la CAM. Cette observation pourrait expliquer la taille réduite des tumeurs, malgré une réponse angiogénique confirmée par des colorations H&E. CONCLUSION : l'hydrogel développé a maintenu une haute viabilité cellulaire et a stimulé l'angiogenèse sur la CAM. Néanmoins, le développement de grandes masses tumorales a été entravé par une intégration hydrogel-tissu limitée, soulignant le besoin d'améliorations pour optimiser l'utilisation de l'hydrogel dans les essais CAM. / INTRODUCTION: The chorioallantoic membrane (CAM) assay is important in cancer research for assessing new drug efficacy by grafting human cancer cells onto the CAM to evaluate tumor growth impact. Despite its utility, limitations include rapid cell proliferation and restricted cell line compatibility. This research project aimed at identifying if hydrogels for molding or 3D printing of cell-containing implants could be coupled to the CAM assay to a) deliver vascular endothelial growth factors (VEGF) and b) to promote the growth of larger cancer cell masses at the CAM. METHODOLOGY: A sodium alginate and hyaluronic acid-based hydrogel, pre-crosslinked with Ca$^{2+}$ ions, was combined with varying proportions of Matrigel®, VEGF, and collagen type I. Rheological, physicochemical, and biocompatibility tests characterized the hydrogel. It was then mixed with HT1080 or HT29 cancer cells, grafted onto the CAM, and incubated at 37 ºC for 7 days. Vascularized cancer cell masses were harvested, and VEGF-induced vascularization was quantified via optical microscopy. Histological examination assessed the cancer cell masses. RESULTS AND DISCUSSION: Cell viability remained above 95% after two days of incubation with the hydrogel. Hydrogels mixed with VEGF and cancer cells induced angiogenesis on the CAM. Unexpectedly, the average weight of vascularized cancer cell masses decreased. Further hematoxylin and eosin (H&E) staining confirmed angiogenic response to the hydrogel implantation, but the limited integration of hydrogels into the CAM, which could help explain the reduced weight of the cell masses harvested after 7 days of growth on the CAM, by comparison to results from the conventional experiments (cells only). CONCLUSION: The hydrogel formulation developed in this study preserved cell viability in vitro and stimulated angiogenesis on the CAM. However, the development of large cancer cell masses remained challenging due to the limited hydrogel-CAM tissue integration after several days of growth on the CAM.

Les protéines de soya constituent un substrat très avantageux pour la formation de systèmes de libération de molécules actives. Les globulines du soya montrent en effet des propriétés fonctionnelles remarquables, notamment gélifiantes, permettant leur utilisation dans la formation d 'hydrogels. Afin de former des gels aux propriétés de libération modulables, la formation de gels de protéines de soya par réticulation a été envisagée. Le présent travail vise à étudier l'impact de la nature de l'agent réticulant employé: le glycéraldéhyde versus le glutaraldéhyde, de leur concentration ainsi que des conditions de formation des gels, plus particulièrement la présence de chlorure de sodium, sur les propriétés macroscopiques des gels, leur microctructure ainsi que leurs propriétés de libération in vitro. Les résultats de ces travaux ont montré que les propriétés macroscopiques étaient très influencées par l'agent réticulant employé, sa concentration ainsi que par la présence de sel lors de la formation des gels. Ainsi, une augmentation du degré de réticulation des gels ou l' aj out de sels durant leur formation conduirait à des changements importants dans les propriétés rhéologiques des gels ainsi que dans leur gonflement. Au contraire, une modification du degré de réticulation des gels et/ ou l'ajout de chlorure de sodium ne conduirait qu'à pas ou peu de changement dans les propriétés moléculaires des gels (structure secondaire des protéines) ou dans leurs propriétés microstructurales, notamment dans la valeur prise par la dimension fractale des flocs composant les gels. Il apparaît donc que la réticulation des globulines de soya conduirait à l'obtention de systèmes aux propriétés macroscopiques modulables mais aux propriétés microscopiques inchangées. Des études de dissolution in vitro ont montré que le degré de réticulation des gels influait sur leurs propriétés de libération. Toutefois, un effet majeur de la charge ionique des molécules piégées au sein du gel ainsi que des conditions physico-chimiques (pH, présence d'enzymes) a été démontré. Par conséquent, si le degré de réticulation des gels ne montre qu'une faible influence sur les phénomènes de libération, les propriétés ioniques de la molécule à libérer et des protéines constituant le gel semblent avoir une importance capitale.

Ces travaux de recherche ont permis d ' élaborer une méthode de gélification 'à froid ' induite par l'addition de sels de calcium à des protéines de soya thermiquement dénaturées, le but ultime étant d'utiliser ces hydrogels dans le développement de nouveaux aliments fonctionnels et comprimés nutraceutiques ayant des effets bénéfiques sur la santé. Les résultats obtenus démontrent la formation de deux types d 'hydrogels distincts selon la teneur en sels de calcium utilisés. À faible teneur en sels de calcium, des hydrogels filamenteux caractérisés par une microstructure ordonnée et une bonne capacité de rétention d'eau sont obtenus, alors que des hydrogels poreux, agrégés et ayant une faible capacité de rétention d'eau sont identifiés lorsqu'une haute teneur en sels de calcium est utilisée. Ces deux types d 'hydrogels démontrent des propriétés rhéologiques distinctes, utilisées pour quantifier leur dimension fractale respective. Il a été démontré par cette étude que les hydrogels de type filamenteux sont sujet à un mécanisme de formation lent selon un patron dicté par l'encombrement stérique des agrégats primaires, tandis que les hydrogels agrégés sont formés rapidement de façon totalement aléatoire, créant une microstructure désordonnée. Des études in vitro en conditions gastro-intestinales montrent clairement la capacité des hydrogels filamenteux et agrégés à protéger des molécules de vitamine B2, emprisonnées dans leur structure, contre les conditions gastriques (enzymes digestives, pH acide) et à les libérer en conditions intestinales. Les hydrogels filamenteux montrent des profils de libération de la vitamine B2 plus constants que ceux agrégés dû à leur structure moins poreuse. Des comprimés formés à partir des hydrogels lyophilisés et compressés ont également été conçus. Les études in vitro effectuées sur ces comprimés démontrent, comme les études menées sur les hydrogels, une bonne protection de la vitamine B2 en présence de conditions gastriques et une libération accrue lorsque soumis aux conditions intestinales. D'intéressantes perspectives dans le développement de véhicules (hydratés ou comprimés) pour la protection de molécules nutraceutiques et leur libération intestinale sont donc envisageables à partir des hydrogels développés dans le cadre de cette étude.

La gélification de deux systèmes mixtes contenant des protéines (P) et du chitosane (CH) a été étudiée par rhéologie. Les systèmes ont été : 1) un mélange d’isolat de protéines de lactosérum (WPI) et CH, et 2) un mélange de gélatine bovine (Gb) et de CH. Les deux systèmes ont été étudiés dans des milieux acides et alcalins à différentes concentrations de polymères. Des gels avec des caractéristiques différentes ont été obtenus avec les deux systèmes dans toutes les conditions étudiées. À concentrations élevées en protéines, le CH a moins d’influence sur les gels formés. Les gels WPI-CH sont de couleur blanche et de texture crémeuse à pH acides, tandis qu’ils sont translucides et élastiques à pH basique. Les systèmes Gb-CH forment toujours des gels translucides, cependant la turbidité augmente à pH 6. Ce travail a permis de comprendre l'effet des concentrations des polymères ainsi que du pH et du type de protéine sur les propriétés rhéologiques des gels P-CH. / The gelation of two mixed systems containing proteins (P) and chitosan (CH) has been studied by rheology. The systems were: 1) a mixture of whey protein isolate (WPI) and CH, and 2) a mixture of bovine gelatin (Gb) with CH. Both systems have been studied in acid and alkaline environment at different polymers concentrations. Gels with different characteristics have been obtained with the two systems in all conditions studied. Chitosan has less influence on the gels at higher protein concentrations. The colour of the WPI-CH gels was white with a creamy aspect at acid pH, whereas they were translucent and elastic at alkaline pH. The Gb-CH systems always formed translucent gels; however the turbidity increases at pH 6. The work presented in this document has allowed the understanding the effect of the polymer concentrations as well as the pH and the type of protein on the rheological properties of the P-CH gels.

Les hydrogels sont des polymères de plus en plus utilisés dans le domaine des biomatériaux. À cause de leur faible différence de densité avec le milieu environnant, ils sont difficiles à visualiser en imagerie par résonnance magnétique (IRM). Des agents de contraste sont couramment utilisés pour faciliter la distinction entre les tissus pendant la visualisation en IRM. L'objectif de ce projet de thèse est donc de développer un agent de contraste paramagnétique et de l'encapsuler dans des hydrogels afin d'en permettre la visualisation en IRM. Des nanoparticules de silice mésoporeuses (MSN) ont été synthétisées et fonctionnalisées avec un agent de contraste cliniquement approuvé, le DTPA-Gd (acide diethylènetriamine pentaacetique complexé avec du gadolinium). Ces nanoparticules ont été caractérisées et leurs propriétés relaxométriques ont été mesurées. Le ratio r2/r1 = 1.46 démontre leur efficacité comme agent de contraste "positif". Ces nanoparticules sont ensuite encapsulées dans des hydrogels biocompatibles par différentes stratégies : dans un hydrogel de poly (éthylène glycol) (PEG) par agitation, ou dans un hydrogel d'alginate par émulsion dans un réacteur. Ces produits ont ensuite été mis en forme, respectivement pour des applications en chirurgie interventionnelle pour des aiguilles de biopsies et en microencapsulation pour le traitement du diabète de type 1. Les performances relaxométriques de l'hydrogel de PEG ont été confirmées par NMRD (Nuclear Magnetic Relaxation Dispersion) à différents champs magnétiques. Cet hydrogel a ensuite été déposé par trempage-retrait sur des substrats de titane simulant des aiguilles de biopsie. Les substrats ont été préalablement lavés et fonctionnalisés avec du phosphate acrylate. En modulant la viscosité à l'aide d'un agent gélifiant, un hydrogel de PEG de 40 à 70 µm d’épaisseur a été obtenu en surface de tubes de titane. Les aiguilles recouvertes ont révélé un contour brillant en IRM. Des séquences d’acquisition en gradient d’écho de moins de 3 min ont permis d’obtenir un rehaussement de signal de 178% par rapport à l’eau. Pour les hydrogels d'alginate, un rehaussement de contraste jusqu'à 113 % a été quantifié par rapport aux billes sans agent de contraste, avec une séquence d'écho de spin de 4 min. Un suivi par IRM sur plusieurs mois a aussi permis de confirmer que les deux hydrogels ne relarguent pas de gadolinium au cours du temps. Ces résultats confirment la possibilité de suivre ces hydrogels à long terme sans perte de signal, ce qui est essentiel à la poursuite de procédures in vivo. Ce travail présente donc des hydrogels paramagnétiques à fort rehaussement de contraste en IRM grâce à l'insertion de nanoparticules de silice mésoporeuses fonctionnalisées avec un agent de contraste. Les résultats obtenus démontrent l'efficacité des MSN-DTPA-Gd encapsulées dans des hydrogels pour visualiser ces derniers par IRM. Ces travaux permettront une visualisation des hydrogels à long terme après implantation dans le corps humain. / Hydrogels are polymers increasingly used in the field of biomaterials. Due to their low density difference with the surrounding middle, they are very difficult to visualize with magnetic resonance imaging (MRI). Contrasts agents are widely used in MRI to differentiate the different biological tissues during the imaging. The main objective of this project was the development of a paramagnetic contrast agent trapped in biocompatible hydrogels enabling their visualization in MRI. Mesoporous silica nanoparticles (MSN) were synthesized and functionalized with a clinically approved contrast agent, DTPA-Gd (gadolinium-diethylenetriamine pentaacetic acid). The nanoparticles were characterized and their relaxometric properties were evaluated. The r2/r1 relaxometric ratio of 1.46 revealed an efficient “positive” MRI contrast agent. Then, different entrapment strategies were performed in biocompatible polymers forming hydrogels: in a poly (ethylene glycol) (PEG) hydrogel (by stirring) or in an alginate hydrogel (by emulsion). These products were designed for applications in interventional surgery for biopsy needles and in microemulsion for type 1 diabetes treatment, respectively. The relaxometric performances of the PEG hydrogel were assessed by NMRD (Nuclear Magnetic Relaxation Dispersion) at different magnetic field strengths. Then, the paramagnetic hydrogel was coated on titanium substrates as substitute of biopsy needles. The substrates were cleaned and functionalized with phosphate acrylate prior to dip-coating. With a thickening agent in the suspension, PEG hydrogels of 40 to 70 µm were deposited on titanium tubes. These samples showed bright outline in MRI. A signal enhancement of 178 %, in regard with water, was obtained with gradient echo sequences shorter than 3 min. For the alginate hydrogels, beads with contrast agent showed a contrast 113 % enhanced, compared to beads without contrast agents, with a spin echo sequence of 4 min. MRI monitoring over months was done to confirm the persistence of the nanoparticles entrapment in both the PEG and alginate hydrogels. These results settled the possibility to use these hydrogels in the long term with no signal decrease, which is essential for in vivo processes. This work introduced paramagnetic hydrogels with a high contrast enhancement in MRI due to the entrapment of mesoporous silica nanoparticles functionalized with a contrast agent. Results confirmed the efficiency of the MSN-DTPA-Gd trapped in the hydrogels to visualize them in MRI. This work could lead to a long term visualization of hydrogels after implantation in the body.

La régulation de l’expression des gènes est ce qui permet à nos cellules de s’adapter à leur environnement, de combattre les infections ou, plus généralement, de produire la quantité exacte de protéine nécessaire pour répondre à un besoin spécifique. Parmi les joueurs les plus importants dans cette régulation de l’expression des gènes on retrouve les microARN (miARN). Ces petits ARN de 22 nucléotides sont présents chez la majorité des espèces multicellulaires et sont responsables du contrôle direct de plus de 30% des gènes exprimant des protéines chez les vertébrés. La famille de miARN lethal-7 (let-7) est composée de miARN parmi les plus connus et ayant des fonctions cruciales pour la cellule. La régulation du niveau des miARN let-7 est essentielle au bon développement cellulaire. La biogenèse de ces miARN, du transcrit primaire jusqu’à leur forme mature, est régulée principalement par Lin28, une protéine pluripotente très conservée. Cette protéine est composée d’un domaine cold shock (CSD) et de deux domaines de liaison au zinc. C’est grâce à ces domaines de liaison à l’ARN que Lin28 peut lier et inhiber la maturation des miARN let-7. L’objectif de cette thèse est de caractériser l’interaction entre Lin28 et le microARN précurseur let-7g afin de mieux comprendre le rôle de cette protéine dans l’inhibition de la biogenèse du miARN. À l’aide de techniques biochimiques et biophysiques, nous avons d’abord défini les principaux déterminants de l’interaction entre Lin28 et la boucle terminale du miARN précurseur let-7g (TL-let-7g). Nous avons conclu que le domaine C-terminal de Lin28, composé d’un motif riche en lysines et arginines ainsi que de deux motifs de liaison au zinc, permet à la protéine de lier spécifiquement et avec haute affinité un renflement riche en guanine conservé chez les précurseurs de la famille let-7. Aussi, parce que la séquence et la spécificité de liaison à l’ARN de ce domaine C-terminal sont semblables à celles de la protéine NCp7 du VIH, nous avons défini ce dernier comme le domaine NCp7-like de Lin28. Par la suite, nous avons caractérisé la multimérisation de trois protéines Lin28 sur la boucle terminale de pre-let-7g. Ceci a permis de réconcilier d’apparentes contradictions retrouvées dans la littérature actuelle concernant les sites de liaison de Lin28 lors de sa liaison aux miARN précurseurs. Nous avons identifié trois sites de liaison à haute affinité sur TL-let-7g qui sont liés dans un ordre précis par trois protéines Lin28. Lors de la formation du complexe multimérique, le CSD permet une déstabilisation de l’ARN, ce qui rend accessible plusieurs sites de liaison. Le domaine NCp7-like permet plutôt un assemblage ordonné de la protéine et facilite la liaison initiale de cette dernière. Ces nouveaux résultats rendent possible la mise au point d’un nouveau modèle de l’interaction entre Lin28 et le miARN précurseur let-7g. En conclusion, les études réalisées dans cette thèse apportent une meilleure compréhension des mécanismes moléculaires impliqués dans la régulation post-transcriptionnelle d’une importante famille de miARN et permettront de guider les futures études dans le domaine de recherche en pleine effervescence qu’est celui de la biogenèse des miARN. / The regulation of gene expression is what allows our cells to adapt to their environment, to fight infections or, more generally, to express the appropriate level of proteins to meet a specific need. The microRNAs (miRNAs) are among the most important players in the regulation of gene expression. These small RNAs of 22 nucleotides are present in most multicellular species and are responsible for the direct control of more than 30% of protein-expressing genes in vertebrates. The miRNA lethal-7 (let-7) family consist of some of the most studied miRNAs and plays crucial roles in the cell. The appropriate regulation of the let-7 miRNAs level is essential for proper cellular development. The biogenesis of these miRNAs, from the primary transcript to their mature form is mainly regulated by Lin28, a highly-conserved pluripotent protein. This protein is composed of a cold shock domain (CSD) and two zinc-binding domains. These RNA-binding domains allow Lin28 to bind and inhibit the maturation of the let-7 miRNA. The objective of this thesis is to characterize the interaction between the Lin28 protein and the let-7g miRNA precursor to better understand the role of this protein in the inhibition of miARN biogenesis. Using biochemical and biophysical techniques, we first identified the main determinants of the interaction between Lin28 and the terminal loop of the precursor miRNA let-7g (TL-let-7g). We concluded that the C-terminal domain of Lin28, composed of a lysine-rich and arginine-rich motif in addition to two zinc-binding motifs, is sufficient to bind with high affinity a conserved guanine-rich bulge located on the TL-let-7g. In addition, because the sequence and RNA-binding specificity of this C-terminal domain are similar to those of the HIV protein NCp7, we defined this region as the NCp7-like domain of Lin28. Subsequently, we characterized the multimerization of three Lin28 proteins on the terminal loop of pre-let-7g. This study helped to reconcile apparent contradictions found in the current literature regarding the Lin28-binding sites on miRNA precursors. We identified three high-affinity binding sites on TL-let-7g that are bound in a stepwise manner by the three Lin28 proteins. As part of the formation of the multimeric complex, both RNA-binding domains of Lin28 play an important role. The CSD destabilizes the RNA and this exposes several binding sites, whereas the NCp7-like domain allows an orderly protein assembly and facilitates the initial binding of the protein. These results lead us to propose a new model for the interaction between Lin28 and pre-let-7g. In conclusion, these studies provide a better understanding of the molecular mechanisms involved in the post-transcriptional regulation of an important family of miRNAs and will help guide future projects in the expanding research area of miRNA biogenesis.

Estudos sistemáticos utilizando a técnica de SAXS foram realizados no síncrotom do LURE (Orsay) com feixe intenso de geometria pontua:, para descrever a cinética e as estruturas obtidas durante as etapas de transformação sol -> gel úmido -> gel seco -> vidros de sílica . As análises foram feitas em termos de uma lei de potência I = q-? cujo expoente está relacionado a dimensão fractal de massa ou de superfície das estruturas. Devido a polidispersividade das unidades espalhadoras as dimensões fractais verificadas podem ser resultados de dimensões reais encobertas por uma distribuição de tamanhos. As curvas obtidas para a cinética de gelificação e envelhecimento dos géis úmidos mostram expoentes que indicam fractalidade de massa e, posteriormente, de superfície. Uma microestrutura composta, que pode resultar de uma agregação limitada por difusão (DLA) seguido de agregação de agregados (C-C) foi observado nas soluções básicas. Por outro lado, os agregados ácidos parecem surgir do crescimento contínuo de cadeias até atingir a interligação com outros agregados com uma cinética que pode ser descrita pelo modelo DLA. No estado de aerogeis outras técnicas como picnometria de mercúrio e hélio, microscopia eletrônica de transmissão e adsorção de gás de nitrogênio, foram também aproveitadas. Nestes materiais encontramos em uma faixa estreita de escala, um expoente indicando fractalidade de massa, embora com superfície lisa. Os resultados estão de acordo com um modelo de estrutura que tem uma matriz de SiO2 densa. A estrutura fractal desaparece durante o tratamento térmico de densificação devido ao rearranjo estrutural. / Systematic SAXS studies have been performed at the LURE synchrotron (Orsay) using an intense beam of point-like cross-section to describe the kinetic and the structure obtained during the sol-> humid gel -> dry gel ->silica glass. The analysis were done in terms of a power law, I = q-? , whose exponent is related to mass and surface fractal dimensions of the structures. Due to polidispersity of the scattering units the found fractal dimensions can be \"smeared\" dimensions that result from a size distribution. All the kinetic and aging humids curves showed evidenced of fractal structures. A composed microstructure that can be originated by clustering of clusters (C-C) of primary units grown by diffusion limited-aggregation (DLA), was observed for basic gels. By other hand, the acidic cluster seems to grow continuously reaching gelation through crosslinking of the clusters. The DLA model seems to describe this process. In the aerogels study others techniques like density measurements using Hg and He, TEM and adsorption of N2 gas were done along with SAXS measurements. Here we could find a narrow range in which the system is a mass fractal, although its surface has been already smoothened. The results agree with a dense SiO2 matrix model. During the densification no fractal structure was verified due to structural rearrangements at high temperature.

The present thesis entitled “Design and Synthesis of Novel Soft Composites from Physical Gels and Nanomaterials” deals with soft materials derived from low molecular weight gels and nanomaterials. Chapter 1 gives a general introduction and overview of the low molecular weight gel (LMOG) which forms the basis of the work. It delves with the history of research in physical gel field, design of different types of gelator molecules, their interesting self-assembly patterns, potential applications of these gelator molecules as well as challenges to design new gelator molecules. It also encompasses the relatively recent area of two component gel system to conveniently bypass the cumbersome synthetic protocol. The aspect of liquid crystallinity in the gel phase is also discussed to throw light on the pattern of assembly and potential uses of these materials. Towards the end there is a comprehensive discussion on the smart nanocomposites derived from LMOGs and nanomaterials. The design, synthesis and numerous applications of inorganic-organic hybrid composites are discussed. Chapter 2A describes the synthesis and characterization of a variety of fatty acid amides of different naturally occurring L-amino acids whose molecular structures are shown in Chart 2A.1. Some of them were found to form gels with various hydrocarbons. The gelation properties of these compounds were studied by a number of physical methods including FT-IR spectroscopy, X-ray diffraction, scanning electron microscopy (SEM), differential scanning calorimetry, rheology and it was found that gelation was critically dependent on the fatty acid chain length and nature of the amino acid. Among them, L-alanine based gelators were found to be the most efficient and versatile as they self-assemble into a layered structure to form the gel network. Mechanisms for the assembly and formation of gels from these molecules are discussed. (Structural formula) Chart 2A.1. Molecular structures of various fatty acid amides of different amino acids. Chapter 2B describes efficient gelation of both aliphatic and aromatic hydrocarbon solvents by a fatty acid amide, n-lauroyl-L-alanine (Chapter 2B.1). In addition, this compound was found to gelate the binary solvent mixtures comprised of aromatic hydrocarbon e.g. toluene and aliphatic hydrocarbon e.g. n-heptane. SEM and AFM showed that the fiber thickness of the gel assembly increases progressively in the binary mixture of n-heptane and toluene with increasing percentage of toluene. The self- Chart 2B.1. Molecular structure of the gelator. assembly patterns of the gels in individual solvents, n-heptane and toluene are however, different. The toluene gel consists of predominantly one type of morphological species while n-heptane gel has more than one species leading to polymorphic nature of the gel. The n-heptane gel is thermally more stable than the toluene gel as evident from the measurement using differential scanning calorimetry. The thermal stability of the gels prepared in the binary mixture of n-heptane and toluene is dependent on the composition of solvent mixture. Rheology of the gels shows that they are shear-thinning material and show characteristic behavior of soft viscoelastic solids. For the gels prepared from binary solvent mixture of toluene and n-heptane, with incorporation of more toluene in the binary mixture, the gel becomes a more viscoelastic solid. The time sweep rheology experiment demonstrates that the gel made in n-heptane has faster gel formation kinetics than that prepared in toluene. Chapter 2C describes lyotropic mesophase formation by organogels of different fatty acid amides of L-alanine in aromatic solvents. The helical assembly, characteristic of the cholesteric mesophase was found to exhibit reflection bands in circular dichroism spectra. The reflection bands corresponded to the pitch of the helical arrangement of the gelator molecules in the aromatic solvent. Transmission Electron Microscopy (TEM) showed presence of twist in the gel fibres. Polarising optical microscopy of the organogel exhibited weak birefringence confirming lyotropic nature of the assembly. Chapter 3 deals with synthesis and characterization of a new class of molecules with molecular structures shown in Chart 3.1. Among a variety of amino acid based molecules only alanine and serine based molecules were found to form translucent gels in aliphatic hydrocarbons such as n-heptane. TEM showed presence of fiber like structures for alanine whereas serine based gelator produces unique network like structures. SEM of the dried gels exhibited presence of three dimensional fibrous networks to spongy globular cauliflower like structures depending on the molecular structure of the gelators. Rheological studies of the organogels showed that they behave like typical LMOG gels. The oscillatory rheological studies demonstrated that the L-serine based gelator, 5 formed more viscoelastic solid like gel than that of L-alanine based gelator, 1 in n-heptane. Chart 3.1. Molecular structures of different amino acid derivatives from 3,4,5-tri-dodecyloxybenzoic acid scaffold. Chapter 4A presents design and properties of new nanocomposites from LMOG and metal nanoparticles (Chart 4A.1). The profound influence of nanoparticle (NP) incorporation into physical gels was evident from various microscopic and bulk properties. The interaction of nanoparticles with the gelator assembly was found to depend critically on the capping agent coating the nanoparticles. TEM showed long range Chart 4A.1. Molecular structures of the gelator and various AuNPs synthesized. directional assembly of the certain AuNPs along the gel fibers. SEM of the dried gels and nanocomposites indicated that the morphological transformation in the composite microstructures depended profoundly on the capping agent of the nanoparticle. Differential Scanning Calorimetry showed that gel formation from sol postponed to lower temperature with incorporation of AuNPs having capping agents which were able to interact with the gel fibers. Rheological studies indicated that the gel-nanoparticle composites exhibit greater rigidity as compared to the naked gel only when the capping agents were able to interdigitate into the gelator assembly. Also, very low percentage of the AuNPs incorporation could switch the cholesteric mesophase of gel assembly, as evident from circular dichroism. We have been able to define a relationship between materials and molecular properties via manipulation of the molecular structures of NP capping agents. Chapter 4B discusses the design and preparation of novel organogel-carbon nanotube composites by incorporation of single-walled carbon nanotubes (SWNT) into physical gels formed by an L-alanine based Low Molecular Mass Organogelator (Chart 4B.1). The gelation process and the properties of the resulting nanocomposites were found to depend on the kind of SWNTs incorporated in the gels. With pristine SWNTs, only a limited amount could be dispersed in the organogels. Attempted incorporation of higher amounts of pristine SWNTs led to precipitation from the gel. To improve their solubility in the gel matrix, a variety of SWNTs functionalized with different aliphatic and aromatic chains were synthesized (Chart 4B.1). Scanning electron microscope images of the nanocomposites showed that the texture and organization of the gel aggregates were altered upon incorporation of SWNTs. The microstructures of nanocomposites were found to depend on the kind of SWNTs used. Incorporation of functionalized SWNTs into the organogels depressed the sol to gel transition temperature, with the n-hexadecyl chain functionalized SWNTs being more effective than the n-dodecyl chain functionalized counterpart. Rheological investigations of pristine SWNT containing gels indicated that the flow of nanocomposites became resistant to applied stress at a very low wt-% of SWNT incorporation. Again, more effective control of flow behavior was achieved with functionalized SWNTs possessing longer hydrocarbon chains. This happens presumably via effective interdigitation of the pendant chains with the fatty acid amides of L-alanine in the gel assembly. Also, the helical cholesteric mesophase formed by the toluene gel could be switched to a layer stacked assembly by doping functional SWNT. Remarkably, by using a near IR laser irradiation at 1064 nm for a short duration (1 min) at room temperature, it was possible to selectively induce a gel-to-sol phase transition of the nanocomposites, while prolonged irradiation (30 min) of the organogel under identical conditions did not cause gel melting. Chart 4B.1. Molecular structures of the gelator and different functionalized SWNT synthesized. Chapter 5A presents design of two component hydrogels and their potential utilization as a template for metal nanoparticle synthesis. Among a variety of acids and amines (Chart 5A.1) only stearic acid or eicosanoic acid when mixed with di- or oligomeric amines in specific molar ratios form stable gels in water. The formation of such hydrogels depends on the hydrophobicity of the fatty acid, and also on the type of amine used. The gelation properties of these two component systems were investigated using electron microscopy, FTIR, 1H NMR spectroscopy, differential scanning calorimetry (DSC) and both single crystal and cast film X-ray diffraction. FTIR spectral analysis suggests salt formation during gelation. 1H NMR of the gels indicates that the fatty acid chains are immobilized in the gel state and when the gel is melted, these chains regain their mobility. Analysis of DSC data indicates that increase in spacer length in the di-/oligomeric amine lowers the gel melting temperature. Two of these gelator salts developed into crystals and structural details of such systems could be secured by single-crystal X-ray diffraction analysis. The structural information of the salts thus obtained was compared with the XRD data of the self-supporting films of those gels. Such analyses provided pertinent structural insight on the supramolecular interactions that prevail within these gelator assemblies. From the crystal structure it is confirmed that the multilayered lamellar aggregates exist in the gel and it also showed that only one plane of symmetry is present in the gel state. Finally, the hydrogel was used as a medium for the synthesis of silver nanoparticles. The nanoparticles were found to position themselves on the fibers and produce a long ordered assembly of gel-nanoparticle composite (Figure 5A.1). Chart 5A.1. Structures and abbreviations of different acids and amines checked for gelation. Figure 5A.1. TEM images of gel-Ag-NP composite. (a) Ag-NP synthesized in hydrogel of SA-IBPA (1:3.5), (b) Magnified images of Ag-NP preferentially residing on gel fibers. Chapter 5B demonstrates the aptitude of supramolecular hydrogel formation using simple bile acids e.g. lithocholic acid (LCA) in aqueous solution containing di- or oligomeric amines (Chart 5B.1). By variation of the choice of the amines in such mixture the hydrogelation properties could be modulated. However, replacement of LCA by cholic acid or deoxycholic acid resulted in no hydrogelation. FT-IR studies show that the carboxylate and ammonium residues of the two components are primarily involved in salt formation. This promotes further assembly of the components reinforced by continuous Chart 5B.1. Structures and abbreviations of different bile acids and amines checked for gelation. hydrogen bonded network leading to gelation. Electron microscopy shows that the morphology of the gels of two component systems which also depends strongly on the amine part. Variation of amine component from the simple ethanediamine (EDA) to oligomeric amine with lithocholic acid changes the morphology of the assembly from long one dimensional nanotubes to three dimensional complex structures. Single crystal X-ray diffraction analysis with one of the amine-LCA complexes suggested the motif of fiber formation where the amines participate with the carboxylate and hydroxyl moiety through H-bonding and electrostatic forces. The rheological properties of this class of two component system provide clear evidence that this system is a shear-sensitive hydrogel and the flow behavior can be modulated varying the acid-amine ratio. From small angle neutron scattering study, it becomes clear that loose gel from LCA-EDA shows scattering oscillation due to the presence of non interacting nanotubules while for gels of LCA with oligomeric amine the individual fibers come together to form complex three dimensional structures of higher length scale.(For structural formula pl refer the pdf file)

La matière molle se consacre à l'étude des propriétés de fluides complexes. Ces fluides diffèrent des fluides simples à cause de l'existence d'une microstructure qui provient de l'arrangement particulier des éléments mésoscopiques constitutifs du matériau (agrégats de particules de noir de carbone, enchevêtrements de polymères, micelles de molécules tensioactives). C'est le couplage entre microstructure et déformation qui confère aux fluides complexes des comportements singuliers et qui engendre des écoulements hétérogènes. Comprendre ces états hors-équilibre et les dynamiques associées présente un intérêt à la fois industriel et fondamental. La rhéologie en cellule de Taylor-Couette est une technique très répandue pour l'étude de la déformation et de l'écoulement de fluides complexes. Cependant, cette méthode n'est pas adaptée à l'étude des écoulements hétérogènes car elle ne fournit qu'une description globale de l'écoulement. Pour pallier ce problème, une technique de vélocimétrie ultrasonore à deux dimensions a été couplée à la rhéologie classique. Cette visualisation locale nous a permis d'étudier l'instabilité inertielle de Taylor-Couette dans les fluides newtoniens, les instabilités élastiques de fluides viscoélastiques (polymères et solutions micellaires), la fluidification de fluides à seuil (gels de noir de carbone, microgels de carbopol et émulsions) et enfin la rupture de gels de protéine soumis à une contrainte de cisaillement. Tous ces exemples montrent des coexistences entre différents états induits par l'écoulement et permettent de revisiter les approches rhéologiques à partir de caractérisations locales des champs de déformation et de vitesse.

Estudos sistemáticos utilizando a técnica de SAXS foram realizados no síncrotom do LURE (Orsay) com feixe intenso de geometria pontua:, para descrever a cinética e as estruturas obtidas durante as etapas de transformação sol -> gel úmido -> gel seco -> vidros de sílica . As análises foram feitas em termos de uma lei de potência I = q-? cujo expoente está relacionado a dimensão fractal de massa ou de superfície das estruturas. Devido a polidispersividade das unidades espalhadoras as dimensões fractais verificadas podem ser resultados de dimensões reais encobertas por uma distribuição de tamanhos. As curvas obtidas para a cinética de gelificação e envelhecimento dos géis úmidos mostram expoentes que indicam fractalidade de massa e, posteriormente, de superfície. Uma microestrutura composta, que pode resultar de uma agregação limitada por difusão (DLA) seguido de agregação de agregados (C-C) foi observado nas soluções básicas. Por outro lado, os agregados ácidos parecem surgir do crescimento contínuo de cadeias até atingir a interligação com outros agregados com uma cinética que pode ser descrita pelo modelo DLA. No estado de aerogeis outras técnicas como picnometria de mercúrio e hélio, microscopia eletrônica de transmissão e adsorção de gás de nitrogênio, foram também aproveitadas. Nestes materiais encontramos em uma faixa estreita de escala, um expoente indicando fractalidade de massa, embora com superfície lisa. Os resultados estão de acordo com um modelo de estrutura que tem uma matriz de SiO2 densa. A estrutura fractal desaparece durante o tratamento térmico de densificação devido ao rearranjo estrutural. / Systematic SAXS studies have been performed at the LURE synchrotron (Orsay) using an intense beam of point-like cross-section to describe the kinetic and the structure obtained during the sol-> humid gel -> dry gel ->silica glass. The analysis were done in terms of a power law, I = q-? , whose exponent is related to mass and surface fractal dimensions of the structures. Due to polidispersity of the scattering units the found fractal dimensions can be \"smeared\" dimensions that result from a size distribution. All the kinetic and aging humids curves showed evidenced of fractal structures. A composed microstructure that can be originated by clustering of clusters (C-C) of primary units grown by diffusion limited-aggregation (DLA), was observed for basic gels. By other hand, the acidic cluster seems to grow continuously reaching gelation through crosslinking of the clusters. The DLA model seems to describe this process. In the aerogels study others techniques like density measurements using Hg and He, TEM and adsorption of N2 gas were done along with SAXS measurements. Here we could find a narrow range in which the system is a mass fractal, although its surface has been already smoothened. The results agree with a dense SiO2 matrix model. During the densification no fractal structure was verified due to structural rearrangements at high temperature.