The aim of this research is to uncover the mechanisms underlying certain basic features of cardiac mechanics. To do so, we will carry out parallel experiments at each of three hierarchical levels of organization: isolated trabeculae, isolated single myofibrils, and isolated myofilaments. The first involves a preparation used in this laboratory for some time. Sarcomere mechanics of isolated cardiac trabeculae can be investigated with high spatial and temporal resolution. The second, single isolated myofibrils, is a preparation recently developed. It has the advantage that every sarcomere in the preparation can be observed, and since sarcomeres are in series, the tension generated by any given sarcomere is that measured at the end of the specimen. Thus, the mechanics of each sarcomere can be established unambiguously. The third preparation is the in vitro motility assay, in which the motion of fluorescently labelled actin filaments can be observed over a lawn of myosin heads planted on a substrate. By combining measurements of velocity and tension, mechanics of filaments can be established. By using these three preparations in parallel experiments, it will be possible to dissect mechanisms underlying basic features of mechanics. We plan to study length-tension relations, deactivation, tension-enhancement, effect of stretch, and other pertinent mechanical phenomena. By observing whether or not a phenomenon shows up at a certain level of structural organization, it will be possible to swiftly rule out certain putative mechanisms. We may then focus more intensely on others. The ability to explore mechanical phenomena at three levels of organization in the same laboratory should permit rapid advance in understanding of the basic principles of cardiac contraction.
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