SYDNEY: A tiny ‘shock absorber’ has been discovered in a type of protein found in the human body, Australian researchers have reported.
A study published in a recent issue of Proceedings of the National Academy of Sciences has investigated tropoelastin – the building block of elastin, which is what gives skin, arteries and lungs their elasticity. Tropoelastin is known for having an odd structure, with a claw-like foot at one end which attaches to cells in the body while a pogo stick-like spring on the other end opens and closes to provide elasticity. For years, scientists have been trying to figure out what the function of the bridge region that connects these two ends is.
Now, a team of researchers have discovered that the bridge in the middle acts like a car’s shock absorber, expanding and contracting to minimise the impact on attached cells, and ensuring that the tropoelastin isn’t ripped off and detached.
“We found it functions as a shock absorber between the two locations and therefore allows for these two different functions and for the two different regions to be connected one to another,” said co-author Tony Weiss from the University of Sydney in New South Wales.
Human ‘shock absorbers’
Previous research has shown how important and extremely durable tropoelastin is. Created mostly before birth and during early childhood, this protein lasts at least 70 years and can also extend up to eight times its normal length and repeatedly return to its original shape.
This function is vital for the human body, because the expansion and contraction of tropoelastin is what allows arteries to pump blood around the body about two billion times in a lifetime.
Despite its importance, the 3-D shape of tropoelastin was defined just last year by Weiss’ team. Finding a curved, spiral-shaped molecule, the team set out to determine the function of the bridge region holding it all together.
Break it and see what happens
To do this, Weiss and colleagues created tropoelastin with mutations in its bridge and compared it to the natural protein to see if the loss of the normal bridge would cause any structural or functional changes. Their results indicated that normal tropoelastin was more porous – it joined together to make elastin faster and it attached to cells more efficiently – indicating the bridge was important for essential functioning.
The team also used small angle X-rays to determine the structure of several natural and mutant tropoelastins. They saw that the mutant proteins were more squashed, while the normal tropoelastin ranged in sizes. A video made from the numerous images taken of the natural protein showed its bridge expanding and contracting, indicating that it is vital for maintaining flexibility and minimising any impact on attached cells.
Regenerative medicine 2.0
By understanding the function of the bridge region, scientists may be able to develop more effective tissue replacements for skin and arteries. These can be damaged by diseases or accidents and often can’t be regenerated naturally, because there is minimal synthesis of tropoelastin after childhood.
“What it’s teaching us is what parts of the protein are important regions to keep. It’s also teaching us we may be able to modify it to function better than is normally seen in living tissues,” said Weiss. “We are using this knowledge to revise and refine what we’re doing.”
It’s hoped that this research can help researchers to optimise the effectiveness of engineered tissues for clinical trials, which patients should benefit from in just a couple of years, said Dietmar Hutmacher, a biomedical scientist from the Queensland University of Technology in Brisbane. “After 15 years of tissue engineering, the era of regenerative medicine 2.0 has begun,” he commented.
Original article in Proceedings of the National Academy of Sciences>
Discovery of tropoelastin structure by Weiss’ team
Tony Weiss’ homepage