How to fold an epithelium

During our everyday life, many of our tissues are subjected to large deformations. LCN scientists have now uncovered how tissues can rapidly adapt their length in response to deformation.

The research, published in Nature Materials, provides us with a better understanding of how the cells within our tissues regulate their mechanical properties for optimal tissue function. This provides insights for engineering of tissues cultured in vitro and allows us to understand how the dramatic shape changes that take place during embryonic development may arise.

In earlier research, the team designed a simple experimental system that allows the generation of free-standing two-dimensional sheets of cells (monolayers) with a thickness of just 10 micrometers – about 1/100 of the width of a human hair. The mechanics of these sheets can be precisely characterised using tests commonly employed in engineering using equipment specially designed by the team. 

For this study, the researchers sought to understand how monolayers react to a sudden decrease in length of about 35%. These levels of deformation mimic, for example, the deformation experienced by our skin when we move a limb. By imaging the monolayers during deformation, they found that the tissues first buckle but then flatten over a period of two minutes – revealing that they can adapt their length remarkably quickly. 

“I was amazed to see the epithelia change their own shape so rapidly, they reduced the first 15% of their length in under 5 seconds! Such speedy movements might be normal for tissues such as muscles but epithelia are usually considered to be more static, or sluggish at least”  explained Dr Thomas Wyatt (UCL, London Centre for Nanotechnology, now at Université Paris-Diderot, France). 

The team then wanted to understand what was happening during the tissue shortening. They first showed that tissues at rest are under tension and that the magnitude of tension correlates with the amount of shortening the tissue can accommodate. 

“We reasoned that it is tension within the monolayer that keeps it flat. So monolayers essentially behave like pre-stressed sheets.” said Dr Jonathan Fouchard (UCL, LCN). 

To test this hypothesis, the team measured tension in the tissue during slow shortening and showed that buckling occurs when tension is dissipated. They further showed that they could predict the threshold of buckling based on the pre-stress and the elasticity of the tissue. 

“Another exciting outcome of our study is that buckles that are created once all stress is dissipated are very stable. This means that tissue shortening may be a way of generating folds in developing organisms.” concluded Professor Guillaume Charras (UCL, LCN and Department for Cell and Developmental Biology). 

The research was led by UCL and carried out in collaboration with scientists from Cambridge University and Université de Grenoble. 

The work was funded through grants from the Biotechnology and Biological Sciences Research Council, the European Research Council, and the Engineering and Physical Sciences Research Council. 


Figure: Shows a time series of images of the monolayer viewed in profile. The two-dimensional tissue sheet is attached to the bars whose position is denoted by the dashed white lines. The cells appear in green and a fluorophore (red) has been added to the medium to allow visualisation of the substrates to which the monolayer is attached. A 35% deformation is applied to the monolayer at t=1s. Immediately after deformation is applied, the tissue takes on an arched shape (see t=2s). Then, the monolayer progressively flattens over the course of ~2 minutes. Scale bar 20 "μ" m.

Other contributors
Nargess Khalilgharibi (UCL); Buzz Baum (UCL); Thomas Wyatt (former LCN)
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