This thesis deals with the differential response of healthy and cancerous cells to surface topography at the nanoscale and the microscale. Using a statistical method we developed we studied the interactions of cells with grooves of nanoscale depth. We demonstrate that healthy cells have a greater ability to align with deeper grooves, whereas cancerous cells are more sensitive to shallow grooves. Analysis reveals that the nucleus follows the alignment of the cell body more closely in cancerous cells, and that the nucleus of cancerous cells is more sensitive to shallow grooves.On microscale pillars we demonstrate for the first time that osteosarcoma cells deform to adopt the surface topography and that the deformation extends to the interior of the cell and in particular to the nucleus. We show that healthy cells only deform during the initial stages of adhesion and that immortalized cells show intermediate deformation between the healthy and cancerous cells. When the spacing between the pillars is reduced, differences in the deformation of different cancerous cell lines are detected. Deformation was also found to be related to the malignancy in keratinocytes, and related to the expression of Cdx2 in adenocarcinoma. The mechanism of deformation is tentatively attributed to the cytoskeleton and attempts to identify the main actors of deformation were performed using confocal microscopy and cytoskeleton inhibitors. Live cell imaging experiments reveal that the deformed cells are very mobile on the surfaces, loss of deformation is necessary for mitosis to occur and deformation after mitosis is more rapid than initial deformation upon adhesion to surfaces.

L'objet de cette thèse est l'étude comparative de la réponse de cellules saines et malignes à la micro- et la nano-topographie de surface. L'interaction avec des stries de profondeur nanométrique est étudiée grâce à une méthode statistique. Nous démontrons que les cellules saines s'alignent plutôt sur des stries profondes, et que les cellules cancéreuses sont plus sensibles aux stries peu profondes. L'analyse des noyaux révèle qu’ils suivent l'alignement des corps cellulaires plus fidèlement dans le cas des cellules cancéreuses et que les noyaux de ces dernières sont plus sensibles aux stries de faible profondeur. Sur des micro-piliers nous démontrons que les cellules d’ostéosarcomes sont capables de se déformer et de faire adopter à leurs noyaux la forme de l'espace entre les piliers. Ceci ne se produit que durant la phase initiale d'adhésion pour les cellules saines. Les cellules immortalisées présentent un niveau intermédiaire de déformation. Quand l'espacement entre piliers est réduit, des différences de déformation sont révélées entre les lignées cancéreuses testées. La déformation est aussi liée au caractère cancéreux de kératinocytes et à l'expression de Cdx2 dans des lignées d'adénocarcinomes. Nous avons tenté d'expliquer ce mécanisme de déformation en l'attribuant au cytosquelette grâce à des analyses en microscopie confocale et avec des inhibiteurs du cytosquelette. L'imagerie de cellules vivantes a permis d'observer que les cellules sont très mobiles même quand elles sont déformées, que la mitose nécessite la perte de la déformation et que la déformation après mitose est plus rapide que la déformation pendant l'adhésion initiale des cellules. / This thesis deals with the differential response of healthy and cancerous cells to surface topography at the nanoscale and the microscale. Using a statistical method we developed we studied the interactions of cells with grooves of nanoscale depth. We demonstrate that healthy cells have a greater ability to align with deeper grooves, whereas cancerous cells are more sensitive to shallow grooves. Analysis reveals that the nucleus follows the alignment of the cell body more closely in cancerous cells, and that the nucleus of cancerous cells is more sensitive to shallow grooves.On microscale pillars we demonstrate for the first time that osteosarcoma cells deform to adopt the surface topography and that the deformation extends to the interior of the cell and in particular to the nucleus. We show that healthy cells only deform during the initial stages of adhesion and that immortalized cells show intermediate deformation between the healthy and cancerous cells. When the spacing between the pillars is reduced, differences in the deformation of different cancerous cell lines are detected. Deformation was also found to be related to the malignancy in keratinocytes, and related to the expression of Cdx2 in adenocarcinoma. The mechanism of deformation is tentatively attributed to the cytoskeleton and attempts to identify the main actors of deformation were performed using confocal microscopy and cytoskeleton inhibitors. Live cell imaging experiments reveal that the deformed cells are very mobile on the surfaces, loss of deformation is necessary for mitosis to occur and deformation after mitosis is more rapid than initial deformation upon adhesion to surfaces.