Uncovering secrets of elastin’s flexibility during assembly

Elastin tubes as substitute arteries
Elastin is a crucial building block in our bodies – its flexibility allows skin to stretch and twist, blood vessels to expand and relax with every heartbeat, and lungs to swell and contract with each breath. But exactly how this protein-based tissue achieves this flexibility remained an unsolved question – until now. An international team has carried out an analysis that reveals the details of a hierarchical structure of scissor-shaped molecules that gives elastin its remarkable properties.

Elastin is characterised by a remarkable combination of flexibility and durability. It is one of the body’s most long-lasting component proteins, with an average survival time comparable to a human lifespan.

During a person’s life, the elastin in a blood vessel, for example, will have gone through an estimated two billion cycles of pulsation.

2D schematic of tropoelastin molecules assembling

A team of researchers at the University of Sydney, MIT (US) and at the University of Manchester (UK) has published in the journal Science Advances an analysis that reveals the details of a hierarchical structure of scissor-shaped molecules that gives elastin its remarkable properties.

Elastin tissues are made up of molecules of a protein called tropoelastin, which are strung together in a chain-like structure.

By combining synchroton imaging, which revealed the shape and structure of the basic tropoelastin molecules, computer modeling and laboratory work, the researchers studied the relationship of the protein structure across different scales, from the sub-molecular level scale up to the scale of a single molecule, thus predicting the dynamics of the molecule.

The dynamics turned out to be complex and surprising, co-author and team-leader Professor Anthony Weiss from the University of Sydney said. "It’s almost like a dance the molecule does, with a scissors twist – like a ballerina doing a dance."

The scissors-like appendages of one molecule naturally lock onto the narrow end of another molecule, like one ballerina riding piggyback on top of the next. This process continues, building up long, chain-like structures.

These long chains weave together to produce the flexible tissues that our lives depend on – including skin, lungs, and blood vessels. These structures assemble very rapidly, and the new research provides insights into the assembly process.

A key part of the puzzle was the movements of the molecule itself, which the research team found were controlled by the structure of key local regions and the overall shape of the protein.

The researchers tested the way this flexibility comes about by genetically modifying the protein and comparing the characteristics of the modified and natural versions. They revived a short segment of the elastin gene that has become dormant in humans, which changes part of the protein's configuration.

They found that even though the changes were minor and just affected one part of the structure, the results were dramatic. The modified version had a stiff region that altered the molecule’s movements. This helped to confirm that certain specific parts of the molecule, including one with a helical structure, were essential to contributing to the material's natural flexibility.

That finding in itself could prove useful medically, the team says, as it could explain why blood vessels become weakened in people with certain disease conditions, perhaps as a result of a mutation in that gene.

While the findings specifically relate to one particular protein and the tissues it forms, the team said the research may help in understanding a variety of other flexible biological tissues and how they work.