| dc.description.abstract | Phagocytosis is a key part of the immune system in which cells identify, ingest and break down foreign particles such as bacteria. Understanding the underlying biophysics of this process is relevant to improving the immune response, tackling various medical conditions and designing micron-sized drug-delivery systems.
The details of phagocytosis are still poorly understood, particularly how cells capture and internalise particles. Cell shape change, membrane remodelling and the
actin cytoskeleton are fundamental parts of the process, and yet their facilitators and coordinators are still to be elucidated. Further, important questions such as how long internalisation takes and the effect of target size and shape are at best only partially understood.
This thesis presents an in-depth investigation into the dynamics of the engulfment stage of phagocytosis, combining vertex modelling, a lattice-based model,
and data analysis. Initial chapters lay the methodological groundwork, introducing
the vertex model and actin lattice model, and detailing model development. Model development is an important part of this study. I aimed to develop a comprehensive model to serve as a framework for researchers employing hybrid vertex-lattice models
in biological systems and process studies.
Data analysis in Chapter 6 employs traditional image analysis techniques on phagocytosis lab videos. This leads to a series of findings detailed in subsequent
chapters, examining experimental data (Chapter 8), target and cell characteristics (Chapters 9 and 10), and intracellular parameters (Chapter 11).
In this study I determine how the rate of internalisation varies with target size, which offers new insights into the efficiency of phagocytosis. Results of this study
suggest that the shape of target particles influences the initiation and completion time of phagocytosis, with implications for designing drug-delivery systems. Moreover, the model predicts a phagocytic capacity for specific cells, and different time of
engulfment for cells with various properties. Also, it is shown that the actin force plays a major role during phagocytosis and that this force is controlled by complex interplay of various intracellular elements.
Finally the discussion chapter integrates these findings into the broader scientific dialogue, comparing them with existing literature and emphasising their contribution to the field. The thesis concludes in Chapter 12, summarising the research journey and its significant discoveries. This study advances our understanding of phagocytosis and provides a foundation for future research in cell biology, offering a robust platform for further exploration and discovery. | en_GB |
