UBC Math Bio Seminar: Nargess Khalilgharibi

Epithelial tissues that line many of the body organs are often formed by a layer of living cells surrounded by the non-living basement membrane (BM). During development and in normal physiology, the organs and their lining epithelial tissues are exposed to different rates and extents of deformation. The tissue’s response to these deformations depends on the mechanical properties of both the cells and the BM. While a plethora of literature exists on cell mechanics, much less is known about BM mechanics. Indeed, many studies consider the BM as a stiff, static substrate. However, like any other polymer network, the structure and mechanical properties of the BM can change. Is the BM a stiff, static network, or is it a dynamic substrate that can contribute to sculpting tissues? Due to its thin, dense, non-fibrillar structure, characterising BM mechanics and its contribution to tissue shape is experimentally challenging. Here, I present two stories where we take a multidisciplinary approach, combining computational modelling at two scales (i.e. tissue and molecular scale) with near super-resolution microscopy and mechanical testing to unravel the role of the BM as a dynamic mechanical structure in defining and maintaining tissue shape.

In the first story, I present a generalised tissue-level Finite Element Model platform that allows testing how BM mechanical properties (e.g. stiffness) influence tissue shape across different geometries and conditions. The platform, which is being developed with a user-friendly interface, is designed for hypothesis testing and experiment design in developmental biology and tissue engineering. In the second story, using the Drosophila wing disc, I show that the tissue retains memory of its shape for up to 4 hours under sustained deformation, enabled by the BM’s initial elasticity. However, prolonged deformation leads to BM network rearrangement and permanent shape change, revealing that the BM sets the long-term viscoelastic timescale of epithelial tissues. We further develop a coarse-grained molecular dynamics model that enables us to relate macroscopic changes in the BM network, quantified using fluorescence microscopy, to microscopic-level structural changes.