For more than 100 years, a basic physiological tenet has ruled cardiac function: A healthy beating heart will pump out the same amount of blood that it receives. Known as the Frank-Starling Law of the Heart, it is as accepted as gravity and, like gravity, is still not fully understood. Using X-ray diffraction techniques, Thomas Irving from Illinois Tech’s College of Science and Pieter de Tombe from Loyola University Chicago Stritch School of Medicine discovered that the protein titin may play a critical role in the nano-science behind Frank-Starling.
Blood enters the heart during its diastolic phase, when cardiac muscle is relaxed and lengthened. As the heart pumps and enters into its systolic phase, the muscle forcefully contracts through the interaction of myosin and actin protein filaments. Titin serves as a kind of elastic band that stores energy when cardiac muscle is stretched and releases energy when the muscle contracts and shortens. Irving and de Tombe learned that the action of titin pulling on the myosin filaments causes changes that ultimately result in increased strength of muscle contraction when muscle is stretched when the heart fills in the diastolic phase.
“The missing piece in all of this is how the one protein talks to the other,” says Irving, whose team’s findings were published in the Proceedings of the National Academy of Sciences (February 23, vol. 113, no. 8). “We have a bunch of candidates in mind and will try to track them down over the next couple of years, at which time we should have a pretty complete story about the Frank-Starling mechanism.”
This past spring the National Institutes of Health awarded Irving, who is also director of the Biophysics Collaborative Access Team (BioCAT), $6.3 million to continue this work and other projects at the Advanced Photon Source.
Watch an IIT Magazine Video Extra featuring Thomas Irving at Argonne National Laboratory.