Normal and malignant cell migration represents a fundamentally important process involved in tissue growth and development, inflammation and cancer metastasis. Leukocyte trafficking from blood into tissues is currently described as a multi-step process that involves initial tethering and rolling, firm adhesion, polarisation and subsequently active locomotion through the vascular endothelium. A specialized leukocyte population com prising T lym phocytes and involved in cell-mediated immunity has a major impact on the overall efficiency of host defence. A number of factors have been previously reported to contribute to the success of directed T cell migration towards effector sites in tissues and organs. These physiological variables include expression of specific cell surface receptor repertoire, chem oattractants and extracellular m atrix com position providing both natural m igration barriers and tissue-specific m icroenvironm ent architecture.

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 o f this study was to quantify the extent of difference in the locomotory response of malignant cells (H U T78 T lym phom a 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 treatm ent and coating conditions. These topographical cues were:​ (i) flat and (ii) m icrogrooved substrates. Furthermore, different cell concentrations were also employed on the same microenvironm ents to investigate the contributory effect of cell-cell interactions. Finally, quantitative differences in locomotory behaviour betw een m alignant HU T78 and normal PBTL cells were calculated utilising a developed theoretical model for two-dim ensional 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 exam ined, although cell-cell interactions were biasing the m gratory response.

The main conclusion of this study is that the two distinctive T cell types investigated do align and m igrate differently on the topographically modified surfaces to which they are exposed and this has been verified by quantitative analysis.