Le travail présenté dans cette thèse est le résultat d'une collaboration fructueuse entre la chimie, la physique et la biologie. En effet, des matériaux avec des propriétés physico-chimiques très contrôlées ont été mis à profit dans le but de caractériser des fonctions cellulaires complexes. Nous présentons tout d'abord la création d'un outil permettant l'étude de la mécanotransduction cellulaire. L'originalité de cet outil est basé sur son activation par étirement permettant de lier réversiblement les cellules à la surface. Nous avons ensuite étudié des comportements de cellules souches et cancéreuses en réponse à des microtopographies sous forme de piliers. Cette approche a permis de définir un comportement cancéreux caractérisé par une déformation prononcée des corps et noyaux cellulaires. Nous montrons aussi que l'utilisation de cette surface couverte de micro-piliers permet de décrire la mécano-biologie de cellules cancéreuses. En effet, ce substrat à topographie contrôlée a permis de montrer que la chimie et la rigidité du substrat n'ont que peu d'incidence sur la déformation des cellules cancéreuses, alors que les éléments du cytosquelette sont primordiaux et que sans eux, la déformation n'est pas possible. Nous avons ensuite inhibé une à une des protéines de l'enveloppe et de la lamina nucléaire afin d'évaluer leur implication dans ces mécanismes de déformation. En parallèle, un séquençage total des ARN (Acides RiboNucléiques) de cellules déformées et non déformées a été réalisé dans le but de visualiser d'éventuelles modifications dans l'expression génique. Ces déformations des cellules cancéreuses entre les micro-piliers ont été comparées à celles que subissent les cellules lors de la traversée de membranes poreuses (Chambres de Boyden). Ces comparaisons nous ont permis d'identifier que plusieurs mécanismes peuvent aboutir à la déformation de cellules cancéreuses et en particulier de leurs noyaux. Nous montrons dans une dernière partie que la mitose cellulaire s'effectue sur les surfaces microstructurées. Nous décrivons une ségrégation des chromosomes qui semble être non parallèle. Toutefois, ces divisions atypiques ne causent pas davantage d'accidents mitotiques. / The work shown in this thesis is the outcome of a successful collaboration between chemistry, physics and biology. Indeed, materials with well controlled parameters have been used in order to characterize complex cellular functions. We first introduce the creation of one tool which allow the study of cells mechanotransduction. The originality of this tool is based on its activation by stretching which allow a reversible adhesion of cells to the surface.Then, we studied the behavior of stem cells and cancerous cells on micropillared surfaces. This approach allowed us to describe a cancerous behavior of cells characterized by strong deformations of cells bodies and nuclei. We also showed that the use of such micropillared surfaces allowed us to describe cancerous cells mecanobiology. Indeed, this substrate with a well controlled topography allowed us to show that substrates chemistry and stiffness have only little effects on cancerous cells deformation while cytoskeleton components are necessary. More specifically, the deformation is impossible without the cytoskeleton. We also inhibited the nuclear envelope proteins and nuclear lamina proteins in order to evaluate their involvement in cells deformation mechanism. In the same time, a total RNA (RiboNucleic Acids) sequencing of deformed and non deformed cells have been done in order to identify an eventual modification in gene expression.These deformations of cancerous cells between micropillars have been compared to the deformation of cells during the transmigration through porous membranes (Boyden chambers). These comparisons allowed us to identify several mechanisms which lead to cells deformation and more specifically to nuclei deformation.We showed in a last part that cells can divide on micropillared surfaces. We described a non parallel like segregation of chromosomes. However, these unusual mitosis didn't lead to supernumerary troubles in cell division.

In this thesis, simulations are performed to study the motion ofindividual cells in flow, focusing on the hydrodynamics of actively swimming cells likethe self-propelling microorganisms, and of passively advected objects like the red bloodcells. In particular, we develop numerical tools to address the locomotion ofmicroswimmers in viscoelastic fluids and complex geometries, as well as the motion ofdeformable capsules in micro-fluidic flows. For the active movement, the squirmer is used as our model microswimmer. The finiteelement method is employed to study the influence of the viscoelasticity of fluid on theperformance of locomotion. A boundary element method is implemented to study swimmingcells inside a tube. For the passive counterpart, the deformable capsule is chosen as the modelcell. An accelerated boundary integral method code is developed to solve thefluid-structure interaction, and a global spectral method is incorporated to handle theevolving cell surface and its corresponding membrane dynamics. We study the locomotion of a neutral squirmer with anemphasis on the change of swimming kinematics, energetics, and flowdisturbance from Newtonian to viscoelastic fluid. We also examine the dynamics of differentswimming gaits resulting in different patterns of polymer deformation, as well as theirinfluence on the swimming performance. We correlate the change of swimming speed withthe extensional viscosity and that of power consumption with the phase delay of viscoelasticfluids. Moreover, we utilise the boundary element method to simulate the swimming cells in astraight and torus-like bent tube, where the tube radius is a few times the cell radius. Weinvestigate the effect of tube confinement to the swimming speed and power consumption. Weanalyse the motions of squirmers with different gaits, which significantly affect thestability of the motion. Helical trajectories are produced for a neutralsquirmer swimming, in qualitative agreement with experimental observations, which can beexplained by hydrodynamic interactions alone. We perform simulations of a deformable capsule in micro-fluidic flows. We look atthe trajectory and deformation of a capsule through a channel/duct with a corner. Thevelocity of capsule displays an overshoot as passing around the corner, indicating apparentviscoelasticity induced by the interaction between the deformable membrane and viscousflow. A curved corner is found to deform the capsule less than the straight one. In addition, we propose a new cell sorting device based on the deformability of cells. Weintroduce carefully-designed geometric features into the flow to excite thehydrodynamic interactions between the cell and device. This interaction varies andclosely depends on the cell deformability, the resultant difference scatters the cellsonto different trajectories. Our high-fidelity computations show that the new strategy achievesa clear and robust separation of cells. We finally investigate the motion of capsule in awall-bounded oscillating shear flow, to understand the effect of physiological pulsation to thedeformation and lateral migration of cells. We observe the lateral migration velocity of a cellvaries non-monotonically with its deformability. / <p>QC 20140313</p>