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Title: Methods for measuring cellular and extracellular matrix biomechanics and its contribution to cancer metastasis
Author: Mason, Louise M.
ISNI:       0000 0004 9356 1287
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2020
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One of the most devastating processes of cancer is metastasis: i.e., the ability of primary tumour cells to migrate and form secondary tumours. Biochemical aspects of cancer are continuously investigated, whereas mechanical aspects of cancer invasion remain largely unexplored. Nonetheless, the importance of mechanics in pathological conditions has been increasingly recognized, underlining the need of novel advanced cell micro-rheology methods. Atomic force microscopy (AFM) is a powerful tool for measuring the mechanical properties of cells under physiological conditions with nanoscale precision. In this thesis, a novel AFM-microrheology method for educing the linear viscoelastic properties of complex materials and cells from stress-relaxation nanoindentation measurements, without the use of preconceived viscoelastic models, nor time consuming experimental procedures, was developed. Using this capability, an investigation into the chemotherapeutic treatment of breast cancer cells was undertaken, unveiling new, mechanical characteristic drug responses. The method is ready to be implemented in conventional AFM setups; providing a simple yet powerful tool to measure dynamic mechanical properties of living cells. Metastasis depends on the ability of cancer cells to migrate between tissue sites. How cells move and exert forces to achieve this is also an important contributor to how this disease spreads. A fast and user-friendly method for traction force microscopy (TFM) was established, and the correlation between cell to extracellular matrix (ECM) forces was studied and utilised as a complementary technique to the AFM-microrheology measurements. This technique uncovered a significant difference in the response of drug treated cancer cells, showing larger forces exerted across cell areas than non-treated cells. Mechanochemically tuneable ECM mimics allow a greater understanding of cell-ECM interactions. Therefore, peptide hydrogels were used as biomimetic substrates to corelate interactions between cancer cells and their environment. The mechanical properties of cells on soft substrates were interpreted by means of a novel, double-layer mathematical model, which found that the traditional Hertzian model underestimates the Young’s modulus of cells. The methods stated above were used to uncover new, quantitative, characteristic mechanical responses of drug-treated, invasive, cancer cells on environments with increasing biochemical and mechanical complexity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Q Science (General) ; R Medicine (General) ; T Technology (General)