Revolutionary discovery could help tackle skin and heart conditions

May 13, 2015, University of Manchester

Scientists at The University of Manchester have made an important discovery about how certain cells stick to each other to form tissue.

The team from the Faculty of Life Sciences studied how cells in the skin and heart are bound together through structures called desmosomes. They wanted to understand how these between the cells in the tissue are so strong.

Desmosomes are specialised for strong adhesion. They bind the together to resist the rigours of everyday life and their failure can result in diseases of the skin and heart, including .

Contrary to popular scientific thinking the researchers revealed a revolutionary finding – that the desmosomes achieve their strength through flexibility rather than rigidity. Their findings have been published in the journal PNAS.

Dr Lydia Tabernero explains the results: "Scientists had always thought the reason for these incredibly strong connections was because the molecules were very rigid and structured as they are in other, weaker intercellular junctions. However, when we isolated desmosome molecules and characterised them we found that they are actually much more flexible than those of the other junctions – the total opposite to what people had thought!"

Desmosomes contain proteins that have extra cellular regions. These form the adhesion that bind the cells to each other and prevent them from separating.

To study their structure Dr Tabernero and her team extracted the proteins and accessed the molecules. Using x-ray scattering, biophysical and computational analyses they were able to build a model of what the molecule looks like and reveal its flexible nature. The molecules are much more ordered than in other intercellular junctions and the ordering is crucial for strong adhesion. Curiously, it is this flexibility that enables them to become ordered.

An idealized array generated with Dsg2 extracellular region structures reproduces the arrangement observed in skin desmosomes. The typical darker desmosomal midline can be visualized by rotation of this array around the vertical axis. Credit: The University of Manchester

Dr Tabernero comments: "What is really fascinating about desmosomes is that they become weaker during wound healing and , and this weakening is necessary to allow to move. In contrast, desmosomes are very strong in adult tissues, particularly in skin and heart. It has been incredibly difficult to work out how they do that but our findings shed new light on this."

She continues: "Conducting this research has been very challenging, but understanding the result was even harder as it went against everything we were expecting. Seeing the flexibility was a big surprise and we had to retest the using different techniques to confirm our findings."

Professor David Garrod has studied desmosomes for decades. He says there are exciting implications for these findings: "This is the first time that any structural information has been reported for desmosome adhesion. Understanding these cell junctions will be important for future biotechnology applications. We also hope our research will contribute to studies into wound healing, cancer and embryonic development."

Explore further: Desmoplakin's tail gets the message

More information: "Cadherin flexibility provides a key difference between desmosomes and adherens junctions." PNAS. DOI: 10.1073/pnas.1420508112

Related Stories

Desmoplakin's tail gets the message

March 2, 2015

Cells control the adhesion protein desmoplakin by modifying the tail end of the protein, and this process goes awry in some patients with arrhythmogenic cardiomyopathy, according to a study in The Journal of Cell Biology.

Protein clue to sudden cardiac death

February 17, 2015

A team led by Oxford University researchers was looking at how a protein, iASPP, might be involved in the growth of tumours. However, serendipitously they found that mice lacking this gene died prematurely of sudden cardiac ...

Cellular 'glue' resists breast cancer

April 20, 2012

Early detection and advances in the treatment for breast cancer have improved the chances of survival, however new avenues for treatment are still needed in the battle against this disease. New research published in BioMed ...

Discovery could improve screening for sudden cardiac death

December 12, 2012

Unfortunately, newspaper articles about young athletes dying suddenly on the field are not unheard of. Such reports fuel discussions about compulsory screening, for example of young footballers, for heart failure. Research ...

Recommended for you

Fish-inspired material changes color using nanocolumns

March 20, 2019

Inspired by the flashing colors of the neon tetra fish, researchers have developed a technique for changing the color of a material by manipulating the orientation of nanostructured columns in the material.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.