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28 THE SCIENTIST | the-scientist.com

CRITIC AT LARGE

© SHUTTERSTOCK.COM, JOSE LUIS CALVO

Titin throws a powerful curveball into the muscle physiology field.

Is it time for a paradigm shift?

BY JULIO M. FERNÁNDEZ

Reimagining Muscle Function

W

atching the elaborate motion of a pitcher throw-

ing a baseball at more than 100 miles an hour

illustrates the essential role of stretching prior

to delivering large amounts of mechanical power. Similarly,

practitioners of the millennia-old practice of yoga often seem

to defy gravity with impressive feats of muscle stretching.

By contrast, astronauts returning to Earth from long voy-

ages display a significant loss of muscle tone, as if the pro-

longed absence of gravitational loading had robbed them of

some essential source of mechanical power. Ye t much of the

biomechanics at the foundation of these familiar phenom-

ena remains beyond the reach of modern scientific inquiry.

Perhaps these gaps will be filled in when we develop a better

understanding of how muscle tissue works.

According to most physiology textbooks, we already fully

understand muscle contraction at the molecular level, and any

further knowledge would only deal with minor details about

the participating molecules specific to different muscle types.

Muscle is a highly organized tissue with a crystal-like arrange-

ment of its filaments. The standard model of muscle contrac-

tion focuses mainly on the sliding of myosin motors along

actin filaments, while other muscle proteins play scaffolding

or regulatory roles. But more recently, physiologists have sug-

gested adding the giant elastic protein titin to the model of the

muscle sarcomere, the basic contractile unit of muscle tissues.

Despite its being the longest continuous polypeptide in the

human body, some medical textbooks still do not include titin

in their description of the sarcomere.

Titin was discovered in the late 1970s by researchers

Koscak Maruyama (J Biochem, 80:405–07, 1976) and Kuan

Wang et al. (PNAS, 76:3698-702, 1979). By its placement

within the muscle sarcomere, it was readily evident that titin

operated under a stretching force during the muscle elonga-

tion that precedes every muscle contraction. But the standard

bulk biochemistry techniques available at the time couldn’t

interrogate this behavior because they lacked the ability to