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Thesis

On two-phase flow models for cell motility

Abstract:

The ability of cells to move through their environment and spread on surfaces is fundamental to a host of biological processes; including wound healing, growth and immune surveillance. Controlling cell motion has wide-ranging potential for medical applications; including prevention of cancer metastasis and improved colonisation of clinical implants. The relevance of the topic coupled with the naturally arising interplay of biomechanical and biochemical mechanisms that control cell motility make it an exciting problem for mathematical modellers.

Two-phase flow models have been widely used in the literature to model cell motility; however, little is known about the mathematical properties of this framework. The majority of this thesis is dedicated to improving our understanding of the two-phase flow framework. We first present the simplest biologically plausible two-phase model for a cell crawling on a flat surface. Stability analyses and a numerical study reveal a number of features relevant to modelling cell motility. That these features are present in such a stripped-down two-phase flow model is notable. We then proceed to investigate how these features are altered in a series of generalisations to the minimal model. We consider the effect of membrane-regulated polymerization of the cell's actin network, the effect of describing the network as viscoelastic, and the effect of explicitly modelling myosin, which drives contraction of the actin network.

Validation of hydrodynamical models for cell crawling and spreading requires data on cell shape. The latter part of the thesis develops an image processing routine for extracting the three-dimensional shape of cells settling on a flat surface from confocal microscopy data. Models for cell and droplet settling available in the literature are reviewed and we demonstrate how these could be compared to our cell data. Finally, we summarise the key results and highlight directions for future work.

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Institution:
University of Oxford
Division:
MPLS
Department:
Mathematical Institute
Research group:
Oxford Centre for Collaborative Applied Mathematics
Oxford college:
Jesus College
Role:
Author

Contributors

Division:
MPLS
Department:
Mathematical Institute
Role:
Supervisor
Division:
MPLS
Department:
Mathematical Institute
Role:
Supervisor
Division:
MPLS
Department:
Mathematical Institute
Role:
Supervisor


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Funding agency for:
Kimpton, LS
Grant:
KUK-C1-013-04


Publication date:
2013
Type of award:
DPhil
Level of award:
Doctoral
Awarding institution:
University of Oxford


Language:
English
Keywords:
Subjects:
UUID:
uuid:93c3cc12-4aac-424d-83bf-3e695efb49fe
Local pid:
ora:7631
Deposit date:
2013-12-09

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