Cell migration and capillary plexus formation in wounds and retinae
Watson, Michael G.
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Cell migration is a fundamental biological phenomenon that is critical to the development and maintenance of tissues in multi-cellular organisms. This thesis presents a series of discrete mathematical models designed to study the migratory response of such cells when exposed to a variety of environmental stimuli. By applying these models to pertinent biological scenarios and benchmarking results against experimental data, novel insights are gained into the underlying cell behaviour. The process of angiogenesis is investigated first and models are developed for simulating capillary plexus expansion during both wound healing and retinal vascular development. The simulated cell migration is coupled to a detailed model of blood perfusion that allows prediction of dynamic flow-induced evolution of the nascent vascular architectures – the network topologies generated in each case are found to successfully reproduce a number of longitudinal experimental metrics. Moreover, in the case of retinal development, the resultant distributions of haematocrit and oxygen are found to be essential in generating vasculatures that resemble those observed in vivo. An alternative cell migration model is then derived that is capable of more accurately describing both individual and collective cell movement. The general model framework, which allows for biophysical cell-cell interactions and adaptive cell morphologies, is seen to have the potential for a range of applications. The value of the modelling approach is well demonstrated by benchmarking in silico cell movement against experimental data from an in vitro fibroblast scrape wound assay. The results subsequently reveal an unexplained discrepancy that provides an intriguing challenge for future studies.