University of Calgary

Clash of the titin

Submitted by tdroden on Wed, 05/02/2012 - 11:22.

Clash of the titin

Research into largest protein may change understanding of how muscles contract
By Don McSwiney

Tim Leonard is winning awards for the innovative use of technology in muscle research. (Photo by Riley Brandt)Tim Leonard is winning awards for the innovative use of technology in muscle research. (Photo by Riley Brandt)

One of the big questions—and there are many —that occupy Killam Scholar and kinesiology researcher Walter Herzog is why a muscle generates more force after it is stretched than a muscle that has not changed length. At the heart of this question is the understanding of how our muscles work. If Herzog and his lab are correct, a new model may be needed.

Researcher Tim Leonard is looking for answers. He’s been part of Herzog’s lab for most of his adult life. He started his undergraduate degree at the University of Calgary when he was 17. Since then, he’s enjoyed a successful, productive and well-decorated academic career.

Leonard is the only individual to win the Canadian Society of Biomechanics Award for his master’s degree and for his PhD. He also won the Western Area Association of Grad Studies Award (an association of American and Canadian Universities from the prairies) and the University of Calgary’s J.B. Hyne Research Innovation Award. These awards recognize innovative research as well as the innovative use of technology.

To study the question of stretched muscle force, Leonard had to devise a way to measure the contractile force of a single myofibril, the microscopic building blocks of our muscles. But how do you grab, stretch and measure the spring of something that is only a few microns long?

The challenge led Leonard to upstate New York and Cornell University, where he found the facilities necessary to construct his nanotechnology micro levers. “It’s kind of one of these things you’d see in a science fiction movie,” says Leonard. “You've got people working in these super-clean rooms, dressed up in these puffy suits with slippers on their feet, and masks so they don’t contaminate the air with their hair or skin cells.”

Leonard points out that he didn’t invent the process he used to create his silicon-nitride cantilevers. The real genius was adapting the existing technology to fit his needs. “I really just said, ‘these should be what I need them to be’ and for me it was really just a stepping stone to get to the actual science and so maybe that’s what the awards were for.”

The cantilevers are incredibly tiny and need to be stored and carried in a sealed case, since the force of wind created just by walking across the room would be enough to snap them instantly.

On the microscope slide, the levers become a powerful tool and helped to suggest that there is another actor at work in the stretched muscle contraction problem—titin, the largest known natural protein.

Despite its size, and the fact that we have a lot of it in our muscles, bio-mechanists aren't exactly sure what titin does. “People have looked at it as a spring, or like a big Slinky, that helps keep the proteins lined up,” say Leonard. “But over the last few years there’s been evidence that titin is not just a passive molecular spring, but that it may actually contribute to active sources.”

Leonard thinks that titin could partially contribute to the increase in force in a stretched muscle. “If titin is actually producing a little bit of what we could call active force, that’s quite novel.”

“Quite novel” is a polite way of saying that Leonard’s award-winning research—as part of Herzog’s team—will likely change or at least amend our understanding of how our muscles contract. “I think we could argue that instead of muscle being a two-filament structure, that maybe there’s a third filament, which is titin, and that titin plays a role that’s not purely passive.”

Understanding the role that titin plays in active force production may one day further our understanding of how diseases like cerebral palsy can be more effectively treated, or how we can more effectively train our athletes to go faster, higher and stronger.