Le procédé de production d’éthanol à partir de biomasse lignocellulosique nécessite l’hydrolyse de cette dernière en sucres simples. Cette hydrolyse est le plus souvent réalisée par voie biologique grâce à des enzymes appelées cellulases. La production de ces enzymes représente cependant un verrou économique majeur au développement du procédé à grande échelle. Les cellulases sont généralement produites industriellement par le champignon filamenteux aérobie Trichoderma reesei, doté d’une forte capacité de sécrétion d’enzymes. Les cultures sont réalisées en bioréacteurs aérés et agités mécaniquement. Elles nécessitent de contrôler la concentration des substrats, ce qui requiert la maitrise de conditions hydrodynamiques et physicochimiques. En effet, le milieu de culture de T. reesei devient une suspension de cellules de champignons associées en filaments, de structure complexe, dont la viscosité augmente avec la concentration microbienne selon un comportement rhéofluidifiant. La viscosité est fonction de la morphologie du microorganisme qui peut, elle-même, varier avec les conditions de cultures. Cet accroissement de viscosité est un critère clef de l’extrapolation du procédé, car il affecte le transfert d’oxygène. Afin de maintenir une concentration en oxygène dissous suffisante, l’agitation et l’aération sont en général augmentées, entraînant un accroissement du cisaillement. Cet accroissement impacte en retour la morphologie du champignon, ralentit sa croissance puis diminue la production de cellulases. Ainsi, les conditions hydrodynamiques et rhéologiques engendrées au sein du bioréacteur sont complexes et variables dans le temps. L’interrelation entre conditions opératoires, morphologie, croissance du champignon et viscosité du moût de fermentation impose l’intégration de tous ces phénomènes pour l’optimisation du procédé, notamment à grande échelle. L’objectif de la thèse est de mettre en place une approche, visant à étudier au laboratoire la croissance de T. reesei et sa production d’enzymes, en reproduisant les contraintes hydrodynamiques associées aux conditions de fonctionnement des fermenteurs industriels. Pour ce faire, deux méthodologies originales ont été développées : une méthode de mesure de la viscosité du milieu, optimisée pour les champignons filamenteux, représentative des conditions rencontrées à grande échelle et qui s’appuie sur l’utilisation d’un rhéomètre rotatif équipé d’un rotor hélicoïdal ; une méthode d’analyse d’images associant un microscope motorisé et des algorithmes d’analyse d’images innovants, qui permet de générer des données sur la morphologie du champignon et d’identifier un critère morphologique pertinent basé sur le nombre de « trous » au sein d’un filament. Parallèlement à ces méthodes, différentes contraintes de cisaillement ont été mises en oeuvre en fermentation, afin de reproduire, à l’échelle du laboratoire, les conditions rencontrées à l’échelle industrielle. Ces outils ont été utilisés conjointement et validés lors de cultures non conventionnelles mimant les conditions industrielles en termes de cisaillement. Ils ont permis d’identifier un critère représentatif du cisaillement (EDCF) et d’établir, à partir de ce critère, des corrélations capables de prédire la viscosité du moût de fermentation, le taux de croissance maximum du microorganisme ainsi que certains paramètres morphologiques de la souche. De façon originale, ces corrélations déterminées à l’échelle du laboratoire ont été validées par des mesures effectuées à l’échelle industrielle. Au final, l’approche développée permet d’identifier au plus tôt les contraintes d’extrapolation à ne pas dépasser, afin d’orienter les choix technologiques des fermenteurs industriels impliquant des champignons filamenteux. / Ethanol production from lignocellulosic biomass requires its transformation into fermentable sugars before the alcoholic fermentation. This step called hydrolysis is catalyzed by cellulases and is often considered as the major technical and economic challenge for the process development. Cellulases are industrially produced by the filamentous fungus Trichoderma reesei, thanks to its high secretion capacity. This fungus is strictly aerobic and is thus cultivated in aerated and stirred bioreactors. The fermentation optimization requires control of physicochemical conditions. Actually the growth of fungi induces an increase of the broth viscosity with shear thinning behavior because of the formation of three-dimensional mycelial structures (from micrometer to millimeter). This viscosity increase has a negative impact on the oxygen transfer. In order to keep the dissolved oxygen concentration higher than a critical limit, it is necessary to increase the power input thereby increasing the shear stress, which may affect the morphology of the fungus as well as its growth and cellulose production. Actually, physico-chemical conditions generated inside the bioreactor are complex and vary with time. These interrelations, between process conditions, morphology, growth and viscosity, require the integration of all these parameters to optimize the full-scale process. The goal of the thesis work was to develop a scale-down approach at lab-scale to mimic hydrodynamic conditions of industrial bioreactors and to study their impact on T. reesei growth and cellulase production. For that purpose, two new tools were developed. The first one consists in a new rheological measurement set-up using a helical rotor dedicated to filamentous fungi preventing mycelium degradation during the measurements. The second one is an original image analyses method that uses specific algorithms. It was then possible to record various morphological data on fungi and to select the most relevant ones (like the number of holes). Meanwhile, a wide range of shear stress conditions were explored in the laboratory bioreactor to reproduce industrial conditions. The new tools we had developed, coupled to these unconventional cultures lead to identifying a shear stress relevant

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This thesis is concerned with the mechanical stress generated in thin layers applied on a substrate. The application takes place at high temperatures and due to different coefficients of thermal expansion of materials, the sample is deformed, and thereby the stress is generated. The first part of the thesis includes the derivation of the Stoney formula for uniaxial and biaxial stress in a layer. Besides, analytical calculations of the normal stress in the layer for the simplified link model, and shear stress on the layer interface were evaluated. The main part of the work consists of solving the problem using FEM modeling. Because the actual temperature behavior during the application was not known, a fictitious temperature load was used as an input. For the samples, the coefficients of thermal expansion of the layer were then searched so that the thermal load resulting deflection corresponds to the experimental data. Three types of models were created, namely the link body model, the axisymmetric model, and the solid model. The axisymmetric model was used for the calculation of samples forming circular isolines during deformation and a volume model for samples forming elliptical isolines. The result of the FEM calculations was the normal stress in the applied layers, for which corresponding relationships were created using regression analysis.

Les interactions cellule-cellule et cellule-matrice extracellulaire (MEC) sont cruciales pour entretenir la cohésion tissulaire. Ces deux types d'adhésions sont fonctionnellement interconnectés par un dialogue permanent qui met en jeu des voies de signalisation convergentes régulant notamment l'architecture et la contractilité du cytosquelette d'acto-myosine sous-jacent. Ce dialogue permet d'établir un équilibre de forces intracellulaires en réponse à la tension appliquée par le milieu extérieur. L'endothélium des vaisseaux sanguins est un tissu soumis à des conditions mécaniques particulières. En plus des compressions intercellulaires subies par tout épithélium, les cellules endothéliales (CEs) doivent également subir et résister aux forces hémodynamiques du flux sanguin et à la rigidité de la lame basale – deux signaux mécaniques agissant de part et d'autre de l'endothélium. Les Cerebral Cavernous Maformations (CCM) ou encore angiomes caverneux sont des lésions vasculaires hémorragiques d'origine génétique qui se développent au niveau des capillaires du système nerveux central et qui se caractérisent par des défauts dans l'environnement proche des CEs. La perte des jonctions intercellulaires et du recouvrement par les cellules murales, l'organisation aberrante de la membrane basale aussi que la stagnation du flux sanguin sont les caractéristiques des CCM. C'est pourquoi nous avons choisi cette pathologie comme modèle intéressant de mécanotransduction mettant en jeu le dialogue entre les intégrines et les cadhérines. En effet, les trois gènes indifféremment mutés dans cette pathologie codent pour des protéines, CCM1-3, qui s'associent en un complexe ternaire et qui sont reconnues comme des acteurs importants de la régulation des jonctions adhérentes. Des études moléculaires et protéomiques montrant que le complexe CCM interagit avec la protéine ICAP-1, un régulateur négatif de l'intégrine β1, nous ont conduit à formuler l'hypothèse selon laquelle ce complexe jouerait un rôle pivot dans la signalisation croisée entre ces intégrines et cadhérines. Les études effectuées pendant ma thèse ont démontré que les protéines CCM régulent l'homéostasie tensionnelle médiée par les structures d'adhérence intercellulaires et à la MEC par leur action inhibitrice sur l'intégrine β1 et en controlant une balance d'activité entre les deux isoformes de ROCK, ROCK1 et ROCK2. Nous avons montré que, suite à la perte des protéines CCMs, la suractivation de l'intégrine β1 augmente la sensibilité des CEs aux signaux mécaniques comme la rigidité de la MEC ou les forces hémodynamiques du flux sanguin. Il en résulte une suractivation de la contractilité cellulaire dépendante de ROCK1 déclenchant une boucle de rétrocontrôle mécanique conduisant à l'amplification des tensions intra- et extracellulaire et brisant ainsi l'homéostasie tensionnelle pour favoriser le phénotype malin. / Cell-cell or cell-matrix interactions have crucial roles in the maintenance of the physical cohesion of any tissue. In addition, growing body of evidence indicates that these two adhesion systems do not act independently, but rather are functionally interconnected by a permanent crosstalk. This dialog usually operates via common molecules that trigger convergent signaling as well as by actomyosin network which, by providing physical link, contributes to establishment of intracellular force counterbalancing tension applied by extracellular surrounding. Blood vessels endothelium is a particular tissue in term of mechanical conditions. Apart from intracellular compression, endothelial lining needs to resist hemodynamic forces as well as rigidity of the basal membrane - two mechanical inputs acting from opposite sides of the endothelial layer. Cerebral Cavernous Malformation (CCM) is a sporadically acquired or inherited disease of venous capillaries within neuro-vascular unit characterized by defects in all aspects of local microenvironment. Loss of intra-endothelial junctions and mural cell coverage, aberrant organization of basal lamina as well as stagnant blood flow are features of CCM lesions. Thereby, CCM became for us an interesting model to study mechanotrasduction process and in this context, the cross-talk between integrin and cadherin mediated adhesion structures. Indeed, CCM proteins are well recognized players involved in a control of VE-cadherin mediated intracellular junctions. In addition, CCM1 was found to interact with ICAP-1, a negative regulator of β1 integrin, raising the possibility that this complex most likely acts as molecular node regulating β1 integrin/ VE-cadherin convergent signaling pathways.Studies performed during this thesis have demonstrated that CCM complex coordinates cadherin- and integrin-mediated tensional homeostasis by repressing β1 integrin activation and maintaining a balance of activity between the two isoforms of RhoA-associated kinases ROCK1 and ROCK2. We have found that β1 integrin sustained over-activation upon CCM proteins loss contributes to increased ECs sensitivity to mechanical cues, such as ECM physical reorganization or hemodynamic force that in turn activates ROCK1-dependent contractility. This establishes a positive feedback mechanical loop that breaks tensional homeostasis and switches on the malignant phenotype.

BCC metals are commonly used throughout the world and understanding their deformation behavior, especially at the sub-grain level, is essential for their continued use in technological advancements. Correctly and confidently characterizing the active slip systems in BCC materials has been a difficult task throughout past research. The research described in this thesis utilizes high resolution digital image correlation (HRDIC) and relative displacement ratio (RDR) analysis to accurately characterize active slip systems in large grained BCC tantalum and provides new insights into dislocation nucleation sites, relative CRSS values for {110} and {112} slip systems, the correlation between GB transmission factors and strain gradients, the relative length of NBGZs, and slip transmission. A 99.99% pure tantalum oligo sample was sputtered with gold and remodeled to provide high resolution data points to be used in HRDIC. The high resolution of the gold remodeled samples combined with a RDR analysis made it possible to confidently identify active slip systems during tensile deformation at room temperature. One of the observations from this analysis was the discrepancy between the observed active slip systems and those predicted from a simple single-CRSS Schmid's Law. By considering the active systems observed in grains with a range of orientation, it was concluded that the {112} slip systems have a higher CRSS than the {110} by 6.7%. Independent CPFE simulations and experiments on single crystal samples of the same material, agreed with our findings establishing a range of increased CRSS for {112} of 3.9%-7.1%. These conclusions are compared with the small number of available estimates of the CRSS ratio, and lie in between the value of equal CRSS used by most modelers, and experimental estimates of 15-25% higher for {112}. The identified active slip systems were also used in the Luster and Morris equation to calculate each GBs transmissivity factor - an estimate of strain incompatibility between neighboring grains. Results indicate that there is an inverse correlation between GB transmissivity and strain gradient slope, as well as a positive correlation between GB transmissivity and slip trace reorientation for some GBs. Only one instance of slip transmission was observed from the 24 GBs analyzed, suggesting it is an uncommon occurrence in BCC tantalum. An analysis of the length of the NBGZ in relation to slip and strain gradients was compared to previous studies and suggests the relative and absolute length of the NBGZ changes with grain size, at least for large length scales. Strain gradients for each side of the GB were measured and results indicated steep negative strain gradient slopes that suggest dislocation nucleation in the GBs and propagation towards the interior of the grain. When compared against the transmissivity factor, an inverse relationship was found to exist between strain gradients and high transmissivity factors.

Les fluides Magnéto-Rhéologiques (MR) de par leurs caractéristiques variant avec le champ magnétique qui leur est appliqué, sont utilisés dans la dissipation d’énergie mécanique. Ainsi, il existe de nombreux dispositifs utilisant ces fluides, par exemple des amortisseurs ou des freins, permettant de contrôler aisément leurs performances. Cependant ces dissipateurs d’énergie mécanique sont amenés à opérer dans des milieux soumis à des perturbations externes notamment des vibrations. Dans le cadre de cette thèse, nous étudions la stabilité des propriétés des fluides magnéto-rhéologiques lorsqu’ils sont perturbés par une stimulation de type vibratoire.Une comparaison analytique de l’ordre de grandeur des efforts vibratoires relativement aux efforts de cohésion magnétique ayant lieu dans le fluide laisse apparaître une possible perturbation du fluide par des vibrations.Nous avons mis en place un banc de test permettant à la fois d’injecter des perturbations vibratoires et de mesurer leur impact sur le fluide utilisé dans un mode classique de cisaillement.Dans certaines conditions, nous avons pu mesurer une diminution de la contrainte de cisaillement du fluide. La variation observée est liée à l’amplitude du mode de déformation de l’élément cisaillant. Trois directions de propagation de vibration selon un repère cylindrique sont étudiées et leurs impacts discutés. La direction normale à la surface est celle qui présente le plus d’effet. La variation maximale de la contrainte de cisaillement observée peut atteindre 40 %. Ce phénomène intervient pour des champs magnétiques faibles, inférieurs à 250 mT, et pour une vitesse de cisaillement faible, inférieure à 100 s-1.Enfin l’effet des vibrations est étudié sur des fluides de différentes viscosités et concentrations de particules, afin d’évaluer l’impact de ces derniers sur la stabilité du fluide / When subjected to a magnetic field, the Magneto-Rheological (MR) fluid increases its apparent viscosity and becomes a viscoelastic solid. They are used in applications requiring dissipation of mechanical energy such as shock absorbers or brakes. These devices operate in environments subject to external disturbances. In this thesis, we study the stability of magneto-rheological fluid properties when they are subjected to vibrations.When comparing the magnitude of the applied forces generated by the vibrations to the magnetic force between the particules it appears that these forces are of the same order. This implies a modification of the fluid behaviour.We developed a dedicated test bench allowing to induce vibration disturbances and to measure their impact on the fluid used in a shear mode configuration.We observed experimentally a decrease in the shear stress of the fluid. This variation depends on the modal deformation of the shearing element. Three propagation directions of vibration according to a cylindrical coordinate are studied and compared. The normal direction to the surface is the one with the most significant effect. The maximum shear stress variation reached was 40%. This phenomenon occurs for low magnetic fields, less than 250 mT, and low shear rate, less than 100 s-1.Finally, the vibration effect is studied on fluids with different viscosities and particle concentrations in order to assess their impact on the fluid’s stability.

The construction industry is closely tied to economic development economies, and increasing demand also presents a significant contribution to environmental degradation. The construction industry’s impact to climate change is led by the 8% contribution from the production of concrete mixtures, more specifically, the production of cement. The combination of using advanced mixdesign techniques (e.g., particle packing models -PPM) and more sustainable ingredients poses as a promising alternative to overcome concrete environmental impact. However, there is a lack of studies regarding the fresh state difficulties arising from the aforementioned combination. Therefore, this work appraises the use of mobility parameters to overcome the fresh state issue raised when mix-designing mortar mixtures through PPM and with high volume of limestone filler. Twelve mixtures were developed with distinct cement content ranging from 150 kg/m3 to 320 kg/m3. To produce sustainable mortar, besides using PPM, cement content was replaced by limestone filler. Time dependent fresh state analysis was performed using mortar slump flow and a rheological profile. In the hardened states, the compressive strength, porosity, surface electrical resistivity tests were performed. The main findings of the project observed a strong correlation between mobility parameters and five distinct rheological parameters: flow behaviour parameter, high shear rate viscosity and shear stress, low shear rate viscosity and shear stress. Additionally, in the hardened state, a dilution parameter IPScement was used to appraise the dilution and filler effect of the mortar mixtures. The works highlighted a promising method to produce eco-efficient mortars.

Indiana University-Purdue University Indianapolis (IUPUI) / Endothelial cells form the lining of the walls of blood vessels and are continuously subjected to mechanical stimuli from the blood flow. Microtubule-organizing center (MTOC), also known as centrosome is a structure found in eukaryotic cells close to the nucleus. MTOC relocates relative to the nucleus when endothelial cells are exposed to shear stress which determines their polarization, thus it plays a critical role in cell migration and wound healing. The nuclear lamina, a mesh-like network that lies underneath the nuclear membrane, is composed of lamins, type V intermediate filament proteins. Mutations in LMNA gene that encodes A-type lamins cause the production of a mutant form of lamin A called progerin and leads to a rare premature aging disease known as Hutchinson-Gilford Progeria Syndrome (HGPS). The goal of this study is to investigate how fluid flow affects the cytoskeleton of endothelial cells. This thesis consists of two main sections; computational mechanical modeling and laboratory experimental work. The mechanical model was implemented using Ansys Workbench software as a tensegrity-based cellular model in order to simulate the state of an endothelial cell under the effects of induced shear stress from the blood fluid flow. This tensegrity-based cellular model - composed of a plasma membrane, cytoplasm, nucleus, microtubules, and actin filaments - aims to understand the effects of the fluid flow on the mechanics of the cytoskeleton. In addition, the laboratory experiments conducted in this study examined the MTOC-nuclear orientation of endothelial cells under shear stress with the presence of wound healing. Wild-type lamin A and progerin-expressing BAECs were studied under static and sheared conditions. Moreover, a custom MATLAB code was utilized to measure the MTOC-nuclear orientation angle and classification. Results demonstrate that shear stress leads to different responses of the MTOC orientation between the wild-type and progerin-expressing cells around the vertical wound edge. Future directions for this study involve additional experimental work together with the improved simulation results to confirm the MTOC orientation relative to the nucleus under shear stress.

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