The proposed experiments are designed to continue to explore the dynamics of sarcomeres in the heart. The specific plans are built largely around a recent discovery: sarcomeres that shorten by 1-2% of their initial length generate substantially more isometric tension than sarcomeres that remain at their initial length throughout contraction. The phenomenon has been labelled shortening-induced force enhancement. The plan is to study the phenomenon in detail, to explore several hypotheses concerning the underlying mechanism, and to determine the impact, if any, on contraction of the heart. Three classes of preparation will be used, each at a different level of organization. At the highest level, single fibers and isolated cardiac trabeculae will be used. At the next level down, sarcomere dynamics will be studied at the level of the single myofibril. Finally, at the most basic level, an in vitro motility assay will be used to study interactions among molecules and filaments. The primary aim in these multi-level experiments is to determine whether the mechanism lies at the molecular level, or at some higher level of organization. Time permitting, a secondary goal is to study additional mechanical phenomena with this unique combination of experimental-approaches. The ability to explore well known features such as the force-velocity relation, the length-tension relation, etc., at the fiber-, myofibril-, and myofilament-level offers an unusual opportunity to approach the mechanisms underlying these features.
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