Role of titin in muscle contraction demonstrated

On the trail of the body’s largest protein: WWU researchers prove the role of titin in muscle contraction

Münster (mfm/mew) - The term "titin" will not mean much to most people - which is actually a pity. Because titin is the largest protein in the body. With its approximately 35,000 amino acids, the muscle protein is huge, but its significance is still poorly understood. Scientists at the Institute of Physiology II of the Westphalian Wilhelms University (WWU) Münster have made it their task to expand knowledge about this special protein. In a study now published in the Journal of the National Academy of Sciences of the USA (PNAS), they were able to use an innovative approach to prove that titin plays a direct role in muscle contraction. These findings could provide a new clue to curing certain muscle and heart diseases.

The subject of the investigations in Wolfgang Linke’s Physiology Institute is the so-called striated musculature. This includes all muscles that we can actively control and move, for example the leg muscles, but also the diaphragm and the heart muscle. Muscle movement requires contraction, which is mediated by thick and thin fibers, also called filaments. This mechanism has been known for some time and has been the subject of a great deal of research. However, as has now been demonstrated in Münster, the protein titin also has an essential role in muscle contraction: titin can be thought of as a spring that holds together the thin and thick filaments in the muscle. When the muscle is stretched, the spring tightens and exerts forces on the filaments.

Dr. Anthony Hessel, lead author of the study, explains the method of investigation: "In order to investigate the effects of titin-induced forces on muscle in more detail, we compared the function of 50 percent of the titin spring molecules in muscle cells before and after they were cut. This revealed that when titin spring force is reduced, the muscle loses significant contractile force." The researchers were able to explain this by showing that the titin tensile force directly affects the tiny molecular myosin motors along the thick filament. The researchers also noticed an effect that challenges previous assumptions about muscle contraction. Prof. Linke explains: "Our studies show that titin not only acts on the thick filaments, but also on the thin ones. This requires some kind of bridge between the thick and thin filaments, which is altered by stretching titin, potentially the myosin-binding protein C."

The investigations required a special X-ray technique with a particle accelerator that emits radiation millions of times stronger than that known, for example, from dentists. To use this technique for their experiments, the scientists traveled several times to the U.S. Department of Energy’s Advanced Photon Source in Chicago. The currently published study is the first part of a series of studies on this topic that will be published next year.

PubMed link to the study