Barrientos, Ricardo;
(2020)
The contribution of the extra-cellular matrix to tissue mechanics and morphology during development.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Extra-cellular matrices are ubiquitous in biological systems, implicated in both mechanics and signalling. The effect of extra-cellular matrix on cell shape in vitro is well established, however much less is known about how the extra-cellular matrix affects tissue morphology in vivo. During development, the extra-cellular matrix surrounding growing tissues must adapt to the changing size and shape of the cellular mass. Physically, whether the extra-cellular matrix contributes to tissue shape depends on the relative mechanical properties between the cells and their extra-cellular matrix. As cells grow, they applya tension to their surrounding extra-cellular matrix; how the extra-cellular matrix responds depends on their comparative stiffness. When the extra-cellular matrix isstiff compared to cells, stress may be generated at their interface as the cells grow. In this case the tissue may change shape to minimise this stress. However, any stress build-up may be relaxed over time by remodelling of the extra-cellular matrix. Biologically, stress may induce signals in the cells, allowing dynamic regulation of cell and extra-cellular matrix mechanical properties. This work is concerned with determining how the extra-cellular matrix contributes to the morphology of a growing tissue, using the wing disc of Drosophila Melanogaster as a model system. The wing disc is a larval-stage, highly proliferative, single-cell thick, epithelial tissue folded into a sac, surrounded by a thin extra-cellular matrix. The mechanical properties of this tissue are inferred using a combination of biophysical and genetic techniques. Relative stiffness of cells and their extra-cellular matrix is experimentally measured using atomic force microscopy. Remodelling rates of the extra-cellular matrix are inferred by measuring turnover rates of its components, either in vitro using fluorescence-recovery, or in vivo using temporal genetic knockdown. By combining these measurements with theoretical models of tissues, the relative importance of stiffness and remodelling to tissue shape can be determined.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The contribution of the extra-cellular matrix to tissue mechanics and morphology during development |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/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 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/10093931 |
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