Impact of multiple scale structural mechanisms on epithelium movement

Abstract

Simple epithelial tissue is formed by individual cells connecting together to form a monolayer sheet. This sheet generates the complex structures of organs by undergoing both large and small scale morphogenic events. Columnar epithelial cells have a height greater than their width and are polarised with a ring of circumferential contractile fibres localised to their apical cell-cell junctions. There has been considerable investigation into the movement of this apical network, especially using lasers to sever individual apical cell edges.

From these apical investigations, a variety of mechanical mechanisms have been suggested to control epithelium movement. However, these mechanisms are contrasting, and are often derived for specific experiments, rather than general apical epithelium movement. Recently, it has been recognised that in additional to the apical network, the entire three-dimensional cell shape impacts epithelium movement. Additionally, there has been growing interest in understanding how epithelium scale movement is controlled by smaller scaler structures, such as contractile fibres.

This thesis utilises both computational and experimental approaches to investigate how the mechanics of underlying structures can drive epithelium scale movement, with a focus on the contribution of individual cells and contractile fibres to apical epithelium movement upon laser severing. These investigations demonstrate that studying the mechanisms of underlying cell and sub cell structures can provide new insights into the causal mechanics of general epithelium movement. It is also shown that inclusion of these mechanisms can lead to greater prediction of epithelium movement.