Relaxation is an important property of muscle activity, but is much less studied or understood than contraction. For skeletal muscle, relaxation is important for motor control of movement, breathing, and posture. For cardiac muscle, relaxation is critically important for diastolic function, allowing effective filling with blood for pumping (systole), during normal activity but especially so when heart rate increases during activity or stress. In both skeletal and cardiac muscle, contraction and relaxation occur in networks of myofibrils organized in parallel bundles (Fig. 1 A). Myofibrils are the subcellular organelles that produce cell and tissue force and shortening. They are composed of sarcomeres which, in turn, are composed of thin and thick filaments that contain the contractile proteins myosin and actin, as well as protein complexes that regulate the switching on and off of contractile activity (Fig. 1 B). Sarcomeres are arranged end to end in series within the myofibrils, with~ 50 in a row in cardiac muscle cells and up to hundreds in a row for skeletal muscle cells. Myofibril relaxation is a complex phenomenon involving both inter-and intrasarcomere components. To study it experimentally requires custom-built apparatus designed to hold on to the small dimensions of myofibrils (1–2 mm width, 40–70 mm length), rapid solution switching, and the ability to monitor picoNewton levels of tension with kinetics in the millisecond timescale. Relaxation of myofibrils from isometric tension occurs in two phases (Fig. 1 C). There is an initial slow, linear phase that is relatively small in amplitude and is thought to reflect the rate of myosin detachment from actin (cross-bridge) detachment. This is followed by a much larger and faster relaxation phase when tension decays to the resting baseline. This phase is thought to reflect multiple compliance components including heterogeneity in cross-bridge detachment within and between sarcomeres, heterogeneity in sarcomere lengths such as shortening of sarcomeres in the middle that stretches sarcomeres at the ends of myofibrils, and series elastic components from proteins such as titin and protein complexes, primarily the Z-disks (1–3).

The complex, multicomponent nature of the fast phase of relaxation, where most of the force decay occurs, has made it difficult to determine mechanisms experimentally. An alternative approach is to develop computational models that account for cross-bridge cycling and detachment, and for the various compliances within and between the sarcomeres of myofibrils. Even this approach has been attempted by few, and none to date have adequately accounted for myofilament compliances as well as intersarcomere compliances along the myofibril. In this edition of the Biophysical Journal, Dr. Kenneth Campbell (4) has made an initial attempt to do just this with computational simulations of relaxation. The model accounts for both cross-bridges and series compliance. Cross-bridges are simulated using the two-state Huxley model, governed by rates for myosin attachment to actin and force (tension) development (f) and a cross-bridge detachment rate (g). Both force and these rates are dependent of the strain in the myosin