Force-sharing among synergistic muscles and mechanical properites of skeletal muscles

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More than half a century ago, A. Huxley developed the cross-bridge theory of muscle contraction, a theory that is represented in current textbooks of anatomy and physiology. According to the cross-bridge theory, muscle shortening occurs through the relative sliding of two sets of filaments, actin and myosin. This sliding is produced by cross-bridges that protrude from the myosin filament, attach cyclically to actin, and pull actin past the myosin filament. Although this theory has served our understanding of how muscles work well, it was known from the very beginning that basic properties of muscle contraction could not be predicted with this theory. Over the past ten years, we have studied these "unexplained" properties and concluded that the two filament thinking of muscle force production needs revision, and that a third filament, the molecular spring titin, needs to be added to our thinking of muscle contraction and force production.The long-term goal of our NSERC supported work is to elucidate the molecular mechanisms of muscle contraction, and the short-term goal is to study the role of structural proteins in muscle force regulation. Specifically in this grant, we will answer five questions involving the structural protein titin. Titin is a molecular spring that provides increasing passive force when muscles are stretched. We believe that titin can change its spring stiffness upon muscle activation, thereby making titin stiffer and stronger when a muscle is actively stretched compared to when it is passively stretched. This stiffening can happen in two basic ways: (i) by a change in titin's inherent stiffness, or (ii) by a change in its free spring length. In this study, we will ask five specific questions aimed at elucidating how titin can change its stiffness upon muscle activation, under what circumstances this occurs, how that affects force regulation in muscle, and how this phenomenon can be incorporated into the current cross-bridge thinking of muscle contraction.This study will provide nano- and macro-biomechanical experiences for trainees and will change the textbook thinking of one of the most basic physiological processes: muscle contraction.