Engineering of Micro-Patterned Protein Scaffolds for the Study of Cancer Cell Behavior

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Examensarbete för masterexamen
Master Thesis
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2016
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Latif, Arsalan
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Cancer is a leading cause of death in the developed world, where up to 90% of cancer related deaths are due to metastasis. Breast cancer accounts for 25% of all cancer related deaths. During metastasis, the cancer cells infiltrate tissues and blood vessels by migration. A better understanding of what drives cancer cells to migrate and how they could be stopped is needed in order to develop more effective drugs that prevent metastasis. It is known that cancer cell behavior is regulated by both physical and chemical external stimuli, and their behavior in two-dimensional (2D) environments is vastly different from three-dimensional (3D) surroundings. Both 2D and 3D surfaces are found in vivo, therefore it is important to evaluate the cell behavior in both 2D and 3D in vitro surfaces. In this study, we assess the behavior of invasive breast cancer cells in a 2D and a 3D matrix by creating nanowrinkled surfaces on and pores in tissue mimicking protein hydrogels. Collagen type I – Hyaluronic Acid (HA) and elastin-like polypeptide (ELP) hydrogels were modified with well-controlled topographical traits. Both the tissue mimicking hydrogels and cancer cell behaviour in their presence were evaluated with non-linear microscopy (NLM) techniques, namely, multi-photon excitation fluorescence (MPEF, autofluoresence and fluorescent stains), coherent anti-Stokes Raman scattering (CARS, chemical contrast based on vibrations) and second harmonic generation (SHG, collagen fibres). The fluorescent stains and MPEF microscopy reveal that the cells adopted either rounded or elongated cell morphology in the porous collagen type I scaffolds, being dependent on the pore diameter. On the contrary, the breast cancer cells did not thrive in the porous ELP scaffolds, possibly the large pore diameter of the porous ELP scaffold did not support the cells to attach fast enough or adverse reaction to the in situ crosslinking. The cells on the ELP nanowrinkled scaffolds adopted elongated morphology and aligned themselves in parallel to the wrinkles. Further, live-cell studies were conducted to observe the effect of the topographical traits on the migration mode of the cells. The morphology of cancer cells on different topographical traits emphasizes the plasticity of cancer cells, and hints towards specific cell migration modes dependent on topographical features.
Beskrivning
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Livsvetenskaper, Biokemi och molekylärbiologi, Cell- och molekylärbiologi, Medicinsk bioteknologi, Life Science, Biochemistry and Molecular Biology, Cell and molecular biology, Medical Biotechnology
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