Soft condensed matter (SCM) systems are ubiquitous in nature. SCM systems contain mesoscopic structures in the size range 10 nm to 1 am that are held together by weak entropic forces. These materials are therefore easily perturbed by external fields such as shear, gravity and electric and magnetic fields and are novel systems for studying non-equilibrium phenomena. The elastic constants of these materials are ≈ 109 times smaller than conventional atomic fluids and hence it is possible to measure the viscoelastic response of these materials using commercial instruments such as rheometers. The relaxation time in SCM systems are of the order of milliseconds as compared to atomic systems where relaxation times are of the order of picoseconds. It is easy to study the effect of shear on SCM, as the shear rates attainable by commercial rheometers are of the order of the inverse of their relaxation times. The dynamics of SCM systems and their local rheological properties obtained using the method of probe diffusion can be quantified through dynamic light scattering experiments. The structure of SCM systems can be quantified using diffraction techniques such as small angle x-ray scattering. In this thesis we report experimental studies on the linear and nonlinear rheology and the dynamics of surfactant cetyltrimethylammonium tosylate (CTAT), which forms cylindrical wormlike micelles, studied using bulk rheology and dynamic light scattering (DLS) technique, respectively. We have also studied the phase behaviour of the ternary system formed by cetyltrimethylammonium 3-hydroxy-napthalene 2-carboxylate (CTAHN), sodium bromide (NaBr) and water using small angle x-ray scattering (SAXS). In Chapter 1, we discuss why SCM systems are suitable for studying non-equilibrium phenomena such as the effect of shear on the structure and dynamics of condensed matter. This is followed by a discussion on the chemical structure, phase behaviour and self assembling properties of the amphiphilic molecules in water. We then discuss the intermacromolecular forces such as van der Waals interaction, the screened Coulomb repulsion and hydrophobic and hydration forces. The systems that have been the subject of our experimental studies, viz. CTAT and CTAHN/NaBr/water have also been discussed in detail. This is followed by a theoretical background of linear and nonlinear rheology, dynamic light scattering and small angle x-ray scattering techniques. Next we describe the stress relaxation mechanisms in wormlike micelles. This is followed by a discussion on some standard techniques of nonlinear time series analysis, in particular the evaluation of the delay time L, the embedding dimension m, the correlation dimension ν and the Lyapunov exponent λ. We have also mentioned a few examples of experimental systems where chaos has been observed. We have also discussed in detail the various routes to chaos namely, the period-doubling route, the quasiperiodic route and the intermittency route. The concluding part of this chapter summarises the main results of the thesis. Chapter 2 discusses the experimental apparatus used in our studies. We have discussed the different components of the MCR-300 stress-controlled rheometer (Paar Physica, Germany). The rheo-small angle light scattering experiments and the direct visualisation experiments done using a home-made shear cell are also discussed. Next we describe the various experiments that can be done using a commercial rheometer. The frequency response and flow experiments have been discussed with some examples from our own work on entangled, cylindrical micelles. This is followed by a discussion on the various components of our dynamic light scattering (DLS) setup (Brookhaven Instruments, USA). Particle sizing of submicrometer colloidal spheres using our DLS setup has been discussed with an example of an angle-resolved DLS study of 0.05µm polystyrene colloids. Next we describe the various components of the SAXS setup (Hecus M. Braun, Austria). As an example application of SAXS we have quantified the structure of the lamellar phase formed by the surfactant CTAHN/water. We finally describe the sample preparation methods employed by us for the different experiments. Our nonlinear rheology experiments on viscoelastic gels of surfactant CTAT (cCT AT= 2wt%) in the presence of salt sodium chloride (NaCl) at various concentrations has been discussed in Chapter 3. We observe a plateau in the measured flow curve and this is attributed to a mechanical instability of the shear banding type. The slope of this plateau can be tuned by the addition of salt NaCl. This slope is due to a concentration difference between the shear bands arising from a Helfand-Fredrickson mechanism. This is confirmed by the presence of a “Butterfly” light scattering pattern in SALS experiments performed simultaneously with rheological measurements. We have carried out experiments at six different salt concentrations 10mM < cN aCl<1M, which yield plateau slopes (α) ranging from 0.07 < α < 0.4. We find that a minimum slope of 0.12, corresponding to a salt concentration of 25mM NaCl, is essential to see a “Butterfly” pattern indicating the onset of flow-concentration coupling at this α value. After this we turn our attention to stress/shear rate relaxation experiments. The remainder of this chapter is split in four parts. We show in Part-I that the routes to rheochaos in stress relaxation experiments is via Type-II intermittency. Interestingly in shear rate relaxation, the route is via Type-III intermittency. We also show that flow-concentration coupling is essential to see the route to rheochaos. This section also brings out the crucial role played by orientational ordering of the nematics during rheochaos using SALS measurements performed simultaneously with rheological measurements. In part-II, we study the spatio-temporal dynamics of the shear induced band en route to rheochaos. Our direct visualisation experiments show that the complex dynamics observed in stress/shear rate relaxation measurements during the route to rheochaos is a manifestation of the spatio-temporal dynamics of the high shear band. In part-III, we describe the results of our stress/shear rate relaxation measurements at a fixed shear rate/stress with temperature as the control parameter and thereby control the micellar length. We see the Type-II intermittency route to rheochaos in stress relaxation measurements and the Type-III intermittency route to rheochaos in shear rate relaxation measurements. We conclude this section by showing the results of linear rheology measurements carried out at different temperatures. We estimate the mean micellar length ¯L, reptation time τrepand the breaking time τbreak. We show that L¯ increases by ≈ 58%, as the sample goes through the route to rheochaos. In Part-I of this chapter we had only qualitatively discussed the correlations between the measured time series of stress and the VH scattered intensity during the Type-II intermittency route to rheochaos. In part-IV we have attempted to quantify the correlations between the two time series using the technique of linear and nonlinear Granger causality. We have also studied the phase space dynamics of the two time series using the technique of Cross Recurrence Plots. We show that there exists a causal feedback mechanism between the stress and the VH intensity with the latter having a stronger causal effect. We have also shown that the bivariate time series share similar phase space dynamics using the method of Cross Recurrence Plots. In chapter 4, we have studied the dynamics of wormlike micellar gels of surfactant CTAT using the DLS technique. We report an interesting result in the dynamics of these systems: concentration fluctuations in semidilute wormlike-micelle solutions of the cationic surfactant Cetyltrimethylammonium Tosylate (CTAT) at wavenumber q have a mean decay rate α qz, with z -̃1.8, for a wide range of surfactant concentrations just above the overlap value c∗. The process we are seeing is thus superdiffusive, like a L´evy flight, relaxing on a length scale L in a time of order less than L2 . The rheological behaviour of this system is highly non-Maxwellian and indicates that the micelle-recombination kinetics is diffusion-controlled (DC) (micelles recombine with their original partners). With added salt (100mM NaCl) the rheometric behaviour turns Maxwellian, indicating a crossover to a mean-field (MF) regime (micelles can recombine with any other micellar end). The concentration fluctuations, correspondingly, show normal diffusive behaviour. The stress relaxation time, moreover is about twenty times slower without salt than with 100mM NaCl. Towards the end of this chapter, we propose an explanation of these observations based on the idea that stress due to long-lived orientational order enhances concentration fluctuations in DC regime. In the previous chapter we had studied the dynamics of wormlike micellar gels of pure CTAT 2wt% and found superdiffusive relaxation of concentration fluctuations due to a nonlinear coupling of long-lived stress and orientational fluctuations to the con- centration. In chapter 5 we present results from dynamic light scattering experiments to quantify the diffusive motion of polystyrene (PS) colloids in the same system. This chapter is split in two parts. In Part-I, we discuss dynamics of PS particles of radius 115 nm and 60 nm in CTAT 2wt%. The radius of the colloidal spheres is comparable to the mesh size ξ = 80 nm of the wormlike micellar network and hence we are probing the network dynamics. We find that ∆r2(t) is wavevector independent at small and large lag times. However at intermediate times, we find an anomalous wavevector dependence which we believe arises from the rapid restructuring of the gel network. This anomalous wavevector dependence of ∆r2(t) disappears as the temperature is increased. In Part-II we discuss the dynamics of PS particles of radius 25 nm and 10 nm, smaller than ξ, in CTAT 1wt% & 2wt%. We once again find an anomalous wavevector dependence of ∆r2(t) at intermediate times for the 2wt% sample. Surprisingly, at large times the particle motion is not diffusive, rather ∆r2(t) saturates. We do not have a clear understanding of this as yet. Also for the 10 nm particle, the motion at small lag times is superdiffusive. The motion of these particles is probably influenced by the superdiffusion of concentration fluctuations observed in pure CTAT 2wt% system (chapter 4). In chapter 6, we report the observation of an intermediate mesh phase with rhom- bohedral symmetry, corresponding to the space group R¯3m, in the ternary system consisting of CTAHN/NaBr/water. It occurs at lower temperatures between a random mesh phase (LDα ) and a lamellar phase (Lα) on increasing the surfactant concentration φs. The micellar aggregates, both in the intermediate and random mesh phases, are found to be made up of a two-dimensional network of rod-like segments, with three rods meeting at each node. SAXS studies also show the presence of small angle peaks corresponding to ad−spacing of 25 nm. Freeze fracture electron microscopy results shows that this peak may correspond to the presence of nodule like structures with no long-range correlations. The thesis concludes with a summary of main results and a brief discussion of the scope for future work in Chapter 7.

This thesis describes an experimental study on fluctuations of a Brownian particle immersed in a fluid, confined by optical tweezers and subject to two different kinds of non-equilibrium conditions. We aim to gain a rather general understanding of the relation between spontaneous fluctuations, linear response and total entropy production for processes away from thermal equilibrium. The first part addresses the motion of a colloidal particle driven into a periodic non-equilibrium steady state by a nonconservative force and its response to an external perturbation. The dynamics of the system is analyzed in the context of several generalized fluctuation-dissipation relations derived from different theoretical approaches. We show that, when taking into account the role of currents due to the broken detailed balance, the theoretical relations are verified by the experimental data. The second part deals with fluctuations and response of a Brownian particle in two different aging baths relaxing towards thermal equilibrium: a Laponite colloidal glass and an aqueous gelatin solution. The experimental results show that heat fluxes from the particle to the bath during the relaxation process play the same role of steady state currents as a non-equilibrium correction of the fluctuation-dissipation theorem. Then, the present thesis provides evidence that the total entropy production constitutes a unifying concept which links the statistical properties of fluctuations and the linear response function for non-equilibrium systems either in stationary or non stationary states.

La première source laser solide à base de polymère dopé par des colorants organiques a été obtenue dans les années 1970, mais jusqu'à la fin du vingtième siècle, peu d'avancées ont été faites. La recherche de sources laser à colorants solides intégrées s'est beaucoup développée ces dernières années grâce à l'avènement de matériaux polymères organiques 'classiques' et hybrides organo-minéraux 'sol-gels' de meilleure qualité.Dans ces travaux, la caractérisation des matériaux est effectuée en termes de propriétés spectrales et de photostabilité des matériaux polymères dopés par des colorants organiques. L'influence sur les propriétés du matériau de l'environnement de la molécule de colorant et du viellissement est discutée.L'application de ces matériaux à la réalisation de sources laser intégrées est faite. Les performances des couples colorant-matrice en terme d'efficacité, de durée de vie en régime de train d'impulsions laser et d'accordabilité en longueur d'onde à l'aide de l'effet de rétroaction distribuée, sont mesurées.Enfin, la comparaison des mesures de caractérisation des matériaux en couches minces et des performances système en régime laser intégré, permet l'identification des paramètres agissant sur ces dernières. Notamment, la présence d'une forte absorption résiduelle dans la bande de fluorescence diminue l'efficacité laser des échantillons, et une bonne conduction thermique dans le matériau permet d'augmenter sa durée de vie en régime laser en limitant la thermodégradation des molécules de colorant. Des compromis sont, de plus, à faire pour la rigidité de la matrice, qui augmente le gain, mais aussi les pertes de propagation dans les matériaux.

Le rampement est un mode de locomotion fondamental de nombreuses cellules eucaryotes, engagé dans des mécanismes aussi importants que embryogenèse, la réponse immunitaire et la cicatrisation. Son dérèglement provoque de graves maladies, en particulier des cancers. La compréhension mécanique de ce mode de locomotion présente également un grand intérêt pour la confection de robots opérant à l'échelle cellulaire. Le schéma classique du rampement cellulaire met en jeu la polymérisation du réseau d'actine dans la partie frontale de la cellule couplée avec l'activation des points d'adhésion focaux liant la cellule à son substrat, alors que la partie postérieure de la cellule se détache du substrat sous l'effet de la contraction engendrée par les molécules de myosine. De manière simplifiée, on peut voir la partie motrice d'une cellule eucaryote comme un gel actif dont les fonctions sont contrôlées par des processus chimiques et mécaniques. En particulier, les mouvements coordonnés de ce gel engendrant le rampement impliquent une auto organisation spatiale et temporelle du cytosquelette et demandent un apport continu d'énergie. Si les bases biochimiques de la motilité cellulaire sont connues, la compréhension qualitative des interactions mécaniques entre les différents acteurs rentrant en jeu dans le rampement n'est que très limitée, et ce malgré les récents efforts visant à construire des modèles complets et exhaustifs du phénomène. Cette thèse présente l'analyse d'un modèle simple et unidimensionnel expliquant le rampement cellulaire. La première partie de la thèse est dédiée à l'analyse inverse du problème d'optimisation en vitesse et en efficacité mécanique du rampement. Notre analyse montre que les distributions optimales de contraintes contractiles et de friction avec le substrat sont en bonnes accord avec les distributions observées. Dans une seconde partie, nous proposons un mécanisme de motilité cellulaire spontanée centré sur la contraction et ignorant la polymérisation et la dépolymérisation de l'actine. A l'origine de la polarisation, l'anti-diffusion auto amplifiée des moteurs pilotant la contraction déstabilise la configuration initialement symétrique de la cellule. L'apparition de cette instabilité morphologique est pilotée par le ratio entre la diffusion et la contractilité des moteurs générant un flot convergent qui, lui-même, transporte les moteurs. Par l'étude unidimensionnelle du phénomène, nous montrons que le flot ainsi produit peut générer un mouvement de translation de la cellule qui reproduit des observations concernant la motilité spontanée des fragments de keratocytes. La troisième partie de la thèse concerne la motilité cellulaire basée sur les propriétés de polymérisation et de dépolymérisation active de l'actine qui permettent non seulement l'autopropulsion de la cellule mais aussi le mécanisme de poussée (d'obstacles) et de tirée (de noyau cellulaire par exemple) de charges données . Nous utilisons un modèle minimaliste pour montrer que la relation force-vitesse dans le cas de la poussée est essentiellement réminiscente du mécanisme de protrusion piloté par la polymérisation alors que la relation force-vitesse du tirage d'une charge ne repose sur le mécanisme de protrusion que pour des charges faibles, le mécanisme de contraction prenant le relais pour des charges plus grandes.

Lab-on-a-chip (LOC) technology has blossomed into a major new technology fundamentally influencing the sciences of life and nature. From a systemic point of view however, microfluidics is still in its infancy. Here, we present the concept of a microfluidic central processing unit (CPU) which shows remarkable similarities to early electronic Von Neumann microprocessors. It combines both control and execution units and, moreover, the complete power supply on a single chip and introduces the decision-making ability regarding chemical information into fluidic integrated circuits (ICs). As a consequence of this system concept, the ICs process chemical information completely in a self-controlled manner and energetically self-sustaining. The ICs are fabricated by layer-by-layer deposition of several overlapping layers based on different intrinsically active polymers. As examples we present two microchips carrying out long-term monitoring of critical parameters by around-the-clock sampling. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

In der Milchindustrie spielt die Auswahl der Starterkulturen eine wichtige Rolle bei der Herstellung fermentierter Produkte mit gewünschter Textur und entsprechenden sensorischen Eigenschaften. Milchsäurebakterien mit der Fähigkeit extrazelluläre Polysaccharide (EPS) zu synthetisieren sind von besonderem Interesse, da auf Grund der in situ gebildeten Hydrokolloide der Einsatz von Zusatzstoffen vermieden werden kann. Die Wirkung von EPS auf die Produkt-eigenschaften ist in der Literatur bereits mehrfach beschrieben, wird jedoch auf Grund der Vielzahl an unterschiedlichen Stämmen und Fermentationsparametern bzw. einer fehlenden Systematisierung immer noch sehr kontrovers diskutiert. Des Weiteren stellt die wissenschaftliche Aufklärung der komplexen Struktur-Funktionsbeziehungen und der Wechselwirkungen mit anderen Produktkomponenten eine große Herausforderung dar. Um die Zusammenhänge besser verstehen zu können, wurde in dieser Arbeit ein neuer Ansatz gewählt: isolierte und aufgereinigte EPS wurden der Milch vor der Säuerung zugesetzt und die daraus hergestellten Milchgele mit jenen mit in situ produzierten EPS verglichen. In Milchgelen aus Einzelstammkulturen von Streptococcus thermophilus oder Lactobacillus delbrueckii ssp. bulgaricus wurden EPS‑Gehalte von 40 - 150 mg/kg ermittelt. Die Gele unterschieden sich hinsichtlich ihrer Viskosität und ihres fadenziehenden Charakters, was erste Hinweise auf die Art der gebildeten EPS liefert. Die Synthese größerer Mengen an EPS zur Charakterisierung und Untersuchung ihrer Funktionalität erfolgte entkoppelt von der Produkt­herstellung mit ausgewählten Stämmen in Batch-Fermentationen mit konstantem pH in komplexen oder semidefinierten Medien. S. thermophilus ST‑143 produzierte ~ 300 mg/L fadenziehende EPS, die durch entsprechende Aufreinigungsschritte als drei EPS‑Fraktionen gewonnen werden konnten: freie EPS (EPSf), kapsuläre EPS (EPSk) und ein Gemisch aus beiden (EPSf+k). EPSf haben eine höhere Molekülmasse (M = 2,6 x 10^6 Da) und eine höhere intrinsische Viskosität (1,14 mL/mg) im Vergleich zu EPSk (M = 7,4 x 10^3 Da, 1,4 x 10^5 Da; intrinsische Viskosität = 0,06 mL/mg) und führten bereits in geringen Mengen zu rheologischen Veränderungen. Allerdings scheinen die EPSk Wechselwirkungen zwischen EPSf Molekülen zu unterstützen. In chemisch gesäuerten Milchgelen konnte durch den definierten Zusatz aufgereinigter Fraktionen von EPSf und EPSf+k vor der Säuerung (c = 0 - 0,35 mg/g) erstmals eine konzentrationsabhängige Wirkung aufgezeigt werden. Mit EPSf stieg der maximale Speichermodul der Milchgele als Maß für die Gelsteifigkeit linear an (457 - 722 Pa). EPSk zeigten hingegen keinen Einfluss. Als Modellpolysaccharid wurde vergleichend das gut beschriebene, ebenfalls ungeladene und nicht gelbildende Homopoly­saccharid Dextran herangezogen (c = 0 - 300 mg/g). EPSf und Dextran veränderten die Gelbildung, erhöhten die Steifigkeit stichfester Gele und die Viskosität gerührter Gele in ähnlichem Maße, es waren jedoch deutlich unterschiedliche Konzentrationen notwendig. Die in den Milchgelen beschriebenen Einflüsse können unter anderem auf Depletionseffekte zwischen gleichgeladenen Polymeren (hier Proteine und Polysaccharide) zurückgeführt werden. / The selection of suitable starter cultures for the production of fermented milk with a desired texture and corresponding sensory attributes is of great importance for the dairy industry. Lactic acid bacteria with the ability to synthesise extracellular polysaccharides (EPS) are of particular interest, because these in situ produced hydrocolloids may allow to omit the use of additives. Many effects of EPS on product properties are already described in the scientific literature, but are still discussed controversially because of the multitude of different strains and fermentation parameters and, hence, a lack of systematisation. Furthermore, research on the mechanisms behind the structure-function relationship and interactions with other product components is a challenging area. To obtain a deeper understanding of this complex system, a new approach was chosen for the present study: EPS were isolated, purified and added to the milk prior to acidification, and the respective milk gels were compared with those with in situ produced EPS. In milk gels acidified by single strains of Streptococcus thermophilus or Lactobacillus delbrueckii ssp. bulgaricus, EPS contents of 40 - 150 g/kg were determined. The gels differed in viscosity and their ropy character, which is a first indicator for the type of the EPS. To allow for their chemical and technofunctional characterisation, the synthesis of higher amounts of EPS was performed by batch-fermentation at constant pH and decoupled from the product manufacturing with selected strains in complex or semidefined media. S. thermophilus ST‑143 synthesised ~ 300 mg/L ropy EPS, which were isolated as three different EPS fractions by applying particular purification steps: free EPS (EPSf), capsular derived EPS (EPSk) and a mixture of both EPS (EPSf+k). EPSf had a higher molecular mass (M = 2.6 x 10^6 Da) and a higher intrinsic viscosity (1.14 mL/mg) compared to EPSk (M = 7.4 x 10^3 Da, 1.4 x 10^5 Da; intrinsic viscosity = 0.06 mL/mg) and affected the rheological properties of aqueous solutions already at low concentration. However, EPSk appear to support interactions between the EPSf molecules. In chemically acidified milk gels a concentration dependent impact of EPSf and EPSf+k, which were added to the milk prior to acidification (c = 0 - 0,35 mg/g), was described for the first time. The maximum of the storage modulus as a measure for stiffness of the milk gels linearly increased with EPSf content (457 - 722 Pa). With EPSk no effects were observed. For the purpose of comparison dextran, a well described also uncharged and non gelling homopolysaccharide, was used as a model polysaccharide (0 - 300 mg/g). EPSf and dextran affected the gelation, increased gel stiffness of set gels and viscosity of stirred gels to a similar way, but the concentrations needed for that found to be completely different. The effects described for milk gels can be ascribed among others to depletion interactions between similar charged polymers (here proteins and polysaccharides).

Nanomedicine is based primarily on the concept of drug formulation through nanotechnology. The main idea is based on the encapsulation of an active ingredient by a nanoparticle (NP) to allow it to accumulate in tumors, to penetrate a biological barrier or to target a biological component. However, the performance of these formulations is disappointing, and, in recent years, it has been noticed that their effectiveness has not improved in the last decade. Some recent hypotheses highlight our lack of knowledge about the interactions of nanotechnologies with living organism and more particularly the lack of techniques to quantify these interactions. We therefore explore in this thesis the development and adaptation of a new microscopy technique, dynamic differential microscopy (DDM), to study the interactions of nanotechnologies with biological matrices. Two subjects are discussed, the first on the interactions of NPs with the proteins of biological fluids and, the second one, on the capacity of NPs to diffuse in interstitial tissues. First, we reviewed quantification techniques that were allowing the measurement of protein adsorption at the surface of NPs. We then identified fundamental questions of this adsorption, namely, if it was generally structured in monolayers or in multilayers and if it was reversible or irreversible. A meta-analysis, based on these questions, could therefore guide the development of the DDM technique to measure protein adsorption and therefore answer these questions. The methodology proposed for the quantification of protein adsorption is based on the measurement of the fluorescence signal which comes from fluorescently tagged proteins adsorbed on non-fluorescent NPs. This methodology was successfully applied for the quantification of the adsorption of lysozyme, albumin and serum proteins. The technique demonstrated that all the proteins studied adsorbed in monolayers and that their adsorption was reversible. An atypical adsorption mechanism which was also hypothesized in our meta-analysis was evidenced by DDM as well. Next, we applied DDM to study the diffusion of NPs in extracellular matrices. The contribution of deformability has been a parameter studied in terms of its relation to improve their diffusion within these confined environments. The diffusion of "soft" NPs was compared to that of "hard" NPs in an agarose gel, mimicking the extracellular matrix. Soft NPs have been observed to diffuse up to 100 times faster than hard NPs of the same size. Evaluation of the hydrodynamic and electrostatic contributions determined that the soft NPs shrinks in the gel, boosting their diffusion in comparison to hard NPs. In summary, this work highlights the important contribution of analytical techniques to the field of nanotechnologies applied to pharmacy and to our understanding of their interactions with living organisms. It is clear that the contribution of these techniques to our detailed understanding of nanomedicine properties has a direct relation with their clinical translation potential. / La nanomédecine repose essentiellement sur le développement de nouvelles formulations pour délivrer les médicaments à partir de nanotechnologies. L’idée principale est que l’encapsulation d’un principe actif par une nanoparticule (NP) pourrait lui permettre de s’accumuler dans des tumeurs, de pénétrer une barrière biologique ou bien pour cibler une composante biologique. Or, les performances de ces « nano-formulations » sont décevantes et, depuis quelques années, il a été remarqué que leur efficacité ne semble pas avoir évoluée dans le temps. De récentes hypothèses mettent de l’avant notre manque de connaissances vis-à-vis les interactions des nanotechnologies avec les éléments du vivant, et plus particulièrement, le manque de techniques robustes permettant de quantifier ces interactions. Nous proposons donc dans cette thèse le développement et l’adaptation d’une nouvelle technique de microscopie, la microscopie différentielle dynamique (DDM), pour étudier les interactions entre les nanotechnologies et les matrices biologiques. Deux thématiques seront abordées, la première, les interactions des NPs avec les protéines des fluides biologiques et, la seconde, la capacité des NPs à diffuser dans des tissus interstitiels. D’abord, nous avons revus les techniques de quantification permettant la mesure de l’adsorption de protéines à la surface des NPs. Nous avons ensuite identifié les questions fondamentales en lien avec cette adsorption. Deux phénomènes sont largement débattus dans la littérature, il s’agit de la formation de multicouches et de la réversibilité de l’adsorption. Une méta-analyse a donc permis d’orienter le développement de la technique par DDM pour mesurer l’adsorption de protéines, dans le but de répondre à ces interrogations. La méthodologie proposée pour la quantification de l’adsorption de protéines à la surface des NPs repose sur la mesure du signal de fluorescence de protéines fluorescentes adsorbées à la surface des NPs non fluorescentes. Cette méthodologie a été appliqué avec succès pour la quantification de l’adsorption des protéines du sérum, du lysozyme et de l’albumine. La technique a d’ailleurs permis de montrer que toutes les protéines étudiées s’adsorbaient en monocouches et que leur adsorption était réversible. Un mécanisme d’adsorption atypique a été mis en évidence dans le cadre de nos expériences et un parallèle a pu être fait avec certaines hypothèses émises avec notre méta-analyse. Ensuite, nous avons appliqué la DDM pour l’étude de la diffusion des NPs dans des matrices extracellulaires. La déformabilité des NPs a été étudiée afin de définir plus précisément sa contribution dans la diffusion à l’intérieur de milieux confinés. La diffusion des NPs « molles » a été comparée à celle des NPs « dures » dans un gel d’agarose, mimant la matrice extracellulaire. Les NPs molles ont été en mesure de diffuser jusqu’à 100 fois plus rapidement que les NPs dures de même taille. L’évaluation des contributions hydrodynamiques et électrostatiques a permis de déterminer que la taille des NPs molles, réduisant dans le gel, leur accordant un avantage diffusif par rapport aux NPs dures. En sommes, ces travaux ont permis de mettre en évidence l’importance des techniques analytiques pour l’étude des nanotechnologies appliquées à la médecine et pour affiner notre compréhension de leurs interactions avec le vivant. Il est clair que la contribution de ces techniques à l’avancement de nos connaissances théoriques relatives aux nanotechnologies aura un impact direct sur leurs chances d’effectuer une transition vers la clinique.

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The ability of the soluble fibre (1->3)(1->4)-β-D-glucan to attenuate postprandial glycemic responses depends on its viscosity which, in turn, depends on molecular weight (MW) and dose. However, the effect of altering viscosity by changing solution volume is unknown. Furthermore, β-glucan solutions may form hard gels when left to age, but the effect of these gels on glycemic responses is unknown. Therefore, the effects of varying the MW and volume of β-glucan solutions and hard gels, on glycemic responses were determined. The results showed that glycemic responses were reduced by increasing viscosity by increasing MW but not by reducing solution volume. Although β-glucan gels reduced the rate of glucose diffusion in vitro, they had no effect on glycemic responses in vivo. Thus, changing solution viscosity through changes in volume does not alter the effect of β-glucan on glycemic response, and β-glucan gels are ineffective at attenuating in vivo glycemic responses.