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Physical Mechanisms for the Emergence of Order in Biological Systems

Strandkvist, C; (2016) Physical Mechanisms for the Emergence of Order in Biological Systems. Doctoral thesis , UCL (University College London). Green open access

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Abstract

How biological order emerges in a robust manner during development is an important question, as the functionality of many tissues depends on the correct spatial arrangement of cells. In this thesis, I consider two examples of ordering, cell sorting and hexagonal packing. In several developing tissues, cells of different type spontaneously self-assemble into domains that are homogenous with respect to cell type both in vitro and in vivo. Current models of sorting assume asymmetry in the physical properties of cell types - either in adhesion, cortical tension or motility. I present a minimal model demonstrating that segregation does not require such asymmetry, but can arise solely from cell motility when this is modelled as a dynamic quantity that changes in response to the composition of the local environment of a cell. Over the course of pupal development, cells in the Drosophila notum rearrange to form a hexagonally packed tissue. How does the tissue transition from disorder to order in an effective and robust way? In particular, how do stochastic fluctuations in junction length contribute to the ordering process? I address these questions by analysing data from live-imaging of the notum using a custom software package I developed. I demonstrate that neighbour exchange events are a consequence of junction fluctuations, rather than being an explicitly regulated and stereotyped process, and I present a mathematical model for how such fluctuations are generated by the stochastic turnover of myosin. I quantify the frequency of neighbour exchange events in embryos with a reduction/overexpression of Myosin II activity and establish that actomyosin is not required for neighbour exchange. In fact, the frequency of neighbour exchange events is inversely proportional to Myosin II levels. The results suggest that the gradual increase in actomyosin during development drives a process akin to annealing that aids tissue ordering.

Type: Thesis (Doctoral)
Title: Physical Mechanisms for the Emergence of Order in Biological Systems
Event: University College London
Open access status: An open access version is available from UCL Discovery
Language: English
Keywords: Biophysics, Computational biology, Epithelium, Tissue ordering
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/1516166
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