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

半个多世纪前，A·赫胥黎提出了肌肉收缩的跨桥理论，这一理论在目前的解剖学和生理学教科书中得到了体现。根据跨桥理论，肌肉缩短是通过肌动蛋白和肌球蛋白两组细丝的相对滑动发生的。这种滑动是由从肌球蛋白细丝伸出的横桥产生的，它周期性地附着在肌动蛋白上，并将肌动蛋白拉过肌球蛋白细丝。虽然这一理论有助于我们理解肌肉是如何工作的，但从一开始就知道，用这一理论无法预测肌肉收缩的基本特性。在过去的十年里，我们研究了这些“无法解释”的性质，得出的结论是，肌肉力量产生的两个细丝思维需要修改，第三个细丝，分子弹簧titin，需要添加到我们对肌肉收缩和力量产生的思维中。我们NSERC支持的工作的长期目标是阐明肌肉收缩的分子机制，短期目标是研究结构蛋白在肌肉力量调节中的作用。具体地说，在这项拨款中，我们将回答五个涉及结构蛋白Titin的问题。Titin是一种分子弹簧，当肌肉拉伸时，它会提供越来越大的被动力。我们相信，Titin可以在肌肉激活时改变其弹簧硬度，从而使Titin在肌肉主动拉伸时比被动拉伸时变得更硬和更强壮。这种刚性可以通过两种基本方式发生：(I)通过改变Titin的固有刚度，或(Ii)通过改变其自由弹簧长度。在这项研究中，我们将提出五个具体的问题，旨在阐明Titin在肌肉激活时如何改变其硬度，在什么情况下发生，如何影响肌肉中的力调节，以及如何将这种现象融入目前肌肉收缩的跨桥思维中。本研究将为受训者提供纳米和宏观生物力学体验，并将改变教科书上对最基本的生理过程之一：肌肉收缩的思考。

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.