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Mechanical Modelling of Tissue Repair in 3-Dimensions

Ioannou, Filippos; (2021) Mechanical Modelling of Tissue Repair in 3-Dimensions. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

The ability to heal wounds is a fundamental survival mechanism exhibited by animals ranging from insects to mammals. The responses that follow epithelial injuries have been studied extensively in various organisms with one of the most popular systems being the Drosophila wing imaginal disc. The wing disc has been used to investigate different aspects of wound healing with a major focus being the biochemical and genetic responses during tissue morphogenesis. There is, though increasing evidence for the significant role that mechanical forces play in the process of wound healing. In this thesis we focus on this mechanical analysis, explored through the development and use of a computational model. Due to the complexity of the biomechanics involved in morphogenetic events, computational approaches have often been used. These have not only allowed essential understanding into the underlying physical phenomena exhibited during wound healing but have also given us the ability to study individual components of complicated systems. Previously, 2-dimensional models have been successful in capturing dynamical properties of the wound healing process in the Drosophila wing disc. However, the 3D structure of the epithelial tissue cannot be ignored. A recent study has shown the Drosophila wing disc to respond to wounding with lateral myosin accumulation, stressing the need for a 3D analysis of the problem, and a 3D computational model. In this thesis, we propose, develop and computationally implement a 3- dimensional hybrid model of the epithelial tissue. We combine the best features of the cell-centred and vertex models, in an attempt to build the most realistic system possible. Our model parameters are subsequently calibrated using experimental observations of 3D cell shape changes during recoil and closure. Finally, we use our validated computational model to study different effects, such as the effect of wound sizes to the healing process and the hypothesised 3D contribution of mechanical forces to efficient wound closure.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Mechanical Modelling of Tissue Repair in 3-Dimensions
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10134021
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