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Abstract
In this thesis we have tested the hypothesis that migration of different T cell types could be influenced by specific topographical geometry of the substrate as one of the contributing microenvironmental factors. Therefore, the objective of this study was to quantify the extent of difference in the locomotory response of malignant cells (HUT78 T lymphoma cell line) and normal peripheral blood T lymphocyte cells (PBTL) to microfabricated surfaces with distinctive custom-produced topographical patterns. Two different surface topographies were implemented to compare the migratory behaviour of these two T cell types under equivalent surface treatment and coating conditions. These topographical cues were: (i) flat and (ii) microgrooved substrates. Furthermore, different cell concentrations were also employed on the same microenvironments to investigate the contributory effect of cell-cell interactions. Finally, quantitative differences in locomotory behaviour between malignant HUT78 and normal PBTL cells were calculated utilising a developed theoretical model for two-dimensional cell migration. The results demonstrate that the HUT78 lymphoma cells have a significant tendency to be more diffusive than the PBTL cells when migrating on topographical surface. By contrast, PBTL cells were faster and more diffusive than HUT78 cells on the flat substrates. Similar results were also found for the two cell concentrations examined, although cell-cell interactions were biasing the migratory response. The main conclusion of this study is that the two distinctive T cell types investigated do align and migrate differently on the topographically modified surfaces to which they are exposed and this has been verified by quantitative analysis.
