Master´s thesis defense by Gertrud Dam-Dalgeir – Niels Bohr Institute - University of Copenhagen

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Master´s thesis defense by Gertrud Dam-Dalgeir

Title: Modelling of Collective Cell Migration

The outer part of the skin is the barrier which separates our interiors from the exterior
world, and is comprised of a thin layer of tightly adhering cells. Inside our bodies, we find similar barriers lining various organs, cavities and blood vessels. Together, these tissues are referred to as the epithelial tissue. The functioning and maintenance of the epithelial tissue is crucial to our health, and therefore if a wound is detected in the epithelium, a healing process immediately starts in which cells collectively and coordinated migrate into the wounded area. The underlying mechanisms which control the collective cell migration process remain elusive, despite the great interest and many efforts invested in understanding this fascinating phenomenon. In this thesis, we view the collective migration of adhering cells as a purely mechanical process, i.e. we neglect the cells’ sensing of biochemical clues, and only include the mechanical forces exchanged between neighbouring cells and between cells and the environment. Using the mathematical formalism of continuum mechanics, we obtain systems of partial differential equations describing the cells in an average manner. Where possible, we relate the macroscopic dynamics to the microscopic interactions. We compare our simulation results with existing motion and density data from an in vitro endothelial
sheet migration experiment conducted at NBI. The simulations are not able to match the experimentally observed features, indicating that the mechanical models are not adequate to describe a real system. Interestingly, a great diversity of experimental observations on migrating cellular sheets is reported in the literature. Some of the reported features are roughly captured by the explored models, indicating that collective cell migration, under certain conditions, indeed can be described by simple mechanical considerations. To elucidate which conditions affect the observed outcome, probably more experiments are needed in which the the system parameters are varied systematically. We hypothesise that e.g. the initial width of the cell colony affects the rate of migration.