Ann-Katrine Vransø West
A thesis for the degree of Doctor of Philosophy defended April 2018.
The PhD School of Science, Faculty of Science, Biocomplexity, Niels Bohr Institute, University of Copenhagen
Professor Lene Broeng Oddershede, Niels Bohr Institute
Professor Janine Erler, Biotech Research & Innovation Centre
Investigation of cancer cell dynamics during division and migration
Cells within biological tissues have two contradicting properties; they possess structure and are resistant towards stresses, while they are also compliant during morphogenesis. The mechanics behind is a well-orchestrated system consisting of both molecular and mechanical pathways. Likewise, cancerous cells are subjected to great forces during cancer progression. It is not known why some cells have invasive potential while others do not, but it is of high interest to discriminate in clinical situations. The work in this thesis tries to uncover some of the differences between non-invasive and invasive cancer cell lines. We have done so using non-invasive techniques such as particle image velocimetry, real-time deformability cytometry, optical tweezers, and theoretical continuum models. Cell divisons in cancerous tissues was found to be short ranged, but graded by the invasive potential of the cell line. Dynamics of cancerous tissue were recapitulated by viscosity based continuum models, and extended to include nematics in assays on kenotaxis. The nematic properties of migrating cell layers provided insight into the underlying dynamics of collective cell migration. We have found that morphological properties affect the deformability of cancer cells, in some cases making non-invasive cell lines more deformable than their invasive counterpart (murine breast cancer). Tracking of granules within cells embedded in 3D collagen matrices of different stiffness, have revealed that invasive cancer cells can adjust to changes in the microenvironment. Measurements of the cells Young’s modulus from real-time deformability cytometry, cooperates the results from viscoelastic experiments. All cells had a Young’s modulus between 2-3 kPa when embedded in a matrix. In contrast, cells grown on glass were found to have a Young’s modulus of 1.4-2.6 kPa. This proves that cells are stiffer when grown on plastic.