Pfannenstill, V. (2019). Nanomotion based antimitotic drug sensitivity screening of cancer cells [Diploma Thesis, Technische Universität Wien]. reposiTUm. https://doi.org/10.34726/hss.2019.50445
The core of this thesis is based on the recent discovery that any living organism is producing nanoscale oscillations (nanomotion). This was discovered by using the atomic force microscope (AFM) in a novel way. Instead of the standard approach in which a specimens surface is scanned, the specimens are directly mounted onto the AFM cantilever. In such a configuration, the cells signal is translated into nano-scale oscillations which can be detected in real time due to the AFMs sensitivity. This novel technique was previously used very successfully to monitor the life or death state of cells. Within the frame of this thesis, we have further explored the potential of nanomotion and used it to monitor more subtle changes within cells. The first chapter of the thesis gives a brief introduction into the general importance of motion as well as into the working principles of AFM explaining also the basic fundamentals of nanomotion detection and main ideas of this thesis. The second part describes the particular experimental setup and cell culturing protocols used in this work. These partially optimized, partially newly developed experimental protocols were successfully applied within the course of this thesis. The third chapter describes in detail the obtained results related to cancer cells and T-lymphocytes. Finally, in the discussion and conclusions chapter a summary of the conducted work and findings is given. Further, the obtained results are compared to previously published data and future perspectives are outlined. This novel technique and the related newly developed protocols allowed us to address some of the most pertinent questions in the fields of cancerology and immunology. We have conducted a detailed study on cancer cells and immune cells demonstrating that our AFM-based technique allows the quantitative differentiation of malignant cancer cells in response to antimitotic drugs and to certain proteins promoting cancer cell motility. In addition, we extended our measurements to also differentiate between resting and activated immune cells. By that, we have shown that our AFM-based mechano-optical assay holds the potential to transform fields like drug discovery and medical diagnostics.
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