Mikrodesenli polimerik sübstratların kanser hücresi davranışı üzerine etkisi

The aim of this study was to develop micropatterned surfaces on biodegradable polymers such as PLGA and PLLA and non-degradable polymer PMMA to study cellular responses including proliferation, cellular morphology, nucleus morphology and deformation, focal adhesions and related pathways, cell division and cycle, and epithelial to mesenchymal transition in cancer cells. An array of nine surfaces decorated with micron sized micropillars were produced using photolithography. Saos-2 osteosarcoma and hOB human osteoblast-like cells were cultured on the micropillar array made from PLGA, PLLA or their blends for focal adhesion and micropillar bending studies. Deformations of nuclei on the micropatterned surfaces were studied with Saos-2, hOB, L-929 mouse fibroblast, SH-SY5Y neuroblastoma, and MCF-7 breast carcinoma cells. Cell division and cycle studies were conducted with Saos-2 cells on PLGA and MDA-MB231 and MCF-7 cells on PMMA. All surfaces induced nucleus deformations but smaller interpillar distances were found to be most effective. Of all the cells tested for nucleus deformations, cancer cells (Saos-2, MCF-7, SH-SY5Y) deformed most prominently. Both Saos-2 and hOB cells were found to apply similar forces to bend pillars and highest bending forces were applied on PLGA and PLLA substrates rather than their blends. Micropatterned PMMA substrates were found to effect cell cycle and induce an arrest at G0/G1 phase. RT-qPCR and RNA sequencing analysis demonstrated that Micropatterned PMMA surfaces induced EMT in epithelial breast cancer cells. Micropatterned substrates were proven to affect many cellular processes and intracellular signaling pathways. Cancer cells were found to be more prone to these changes.Ph.D. - Doctoral Progra