Modelling doming in epithelial monolayers

A problem presented at the VPH NoE SG Nottingham 2009.


Presented by:
Dr Paul Appleton (Cell and Developmental Biology, University of Dundee)
Dr Zhuoyu Li (Cell and Developmental Biology, University of Dundee)
Prof Inke Näthke (Cell and Developmental Biology, University of Dundee)
P Appleton, J Fozzard, OE Jensen, GW Jones, JR King, Z Li, A Lovrics, I Näthke, M Nelson, I Pu

Problem Description

MDCK and other cultured epithelial cells form “domes” when grown on rigid substrates in confluent monolayers. Domes are formed by cells that lift up from the solid support but remain continuous with the monolayer. There is a paucity of data available about the cellular pathways that control this process. When grown on flexible, semi-permeable filters, domes are not formed. The activity of the Na+/K+-ATPase is crucial for dome formation suggesting that ion transport and associated water flow are important.

We have monitored domes over many hours in MDCK cell cultures and found that domes grow, collapse, and usually re-form in the same place. We have data for inhibitors that do and do not alter this behaviour. We also know that light can “poison” dome formation. Interestingly we created mutant cells that form vary domes of different size and dynamics. These mutant cells only differ in the expression of a fluorescent protein we introduced stably.

The challenge I would like to pose to the group is to develop a model that describes doming behaviour using the provided movies as source for information about the physical dimensions of domes relative to cells, the speed and patterns of re-arrangements that accompany dome formation. The model should take into account cellular parameters that have to be altered to generate different doming behaviour in the two mutants. The kinds of parameters that should be included in the model are cell-cell and cell-substrate adhesion, the permeability of the cellular junctions, cellular stretchiness (for lack of a better term). Another question that is relevant in this context is whether, or in what way cells surrounding a dome are different from those further away or in it. Understanding the physical properties thatare involved will allow us to identify and validate cellular pathways that are involved in tissue shape changes.

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