AbstractA complex system is a collection of parts, that can be identical or different, that interact with each other and environment, and exhibit emergent behaviour. Here, I consider the formation of vascular structures in the body as a complex system consisting of an emergent pattern in interacting endothelial cells. A cancer tumour is a different but related complex system that contains various types of cells, some of which having cancer-inducing mutations. To understand the formation of a vascular structure or a cancer tumour, it is important to understand both the single cells and cell-cell interactions.
To study the physical interaction among cells in vascular formation or cancer cell growth, in this thesis an agent-based model is built based on the physical properties of cells which includes the size, shape, direction, and position of cells. In this way the mathematical equations in the model can show the physical variation among modelled cells. The 3-dimensional shape of cells is modelled, and so while I start with cell interactions in petri-dish the model can be easily extended to describe motility of cells in a 3-dimensional system in the future.
The physical model is implemented and then simulated with in silico experiments, and then the spatial distribution of cells in in vitro experiments is analysed and used to calibrate the model. In vitro experiments with and without a drug in normal and hypoxic conditions are carried out. Also the patterns formed by cells with different treatment are analysed to produce different parameter combinations in the model.
This physical model is shown to be able to predict vessel formation and be reused to predict the spatial distribution of cancer cells in in vitro growth experiments. With biological data such as cell size, cell shape, etc. this model is able to predict behaviours of various cell types, and can also be used to predict more complex phenomena, such as mixed type of cancer cells growing in 3-dimensions with vascular structures
|Date of Award||Nov 2015|
|Supervisor||James Bown (Supervisor) & Jiujiang Zhu (Supervisor)|
- Cell-cell interaction