Development and Experimental Verification of the Distribution-Moment Model of Muscle

9318631扎哈拉克在本申请中提出的研究涉及对骨骼肌动力学的定量理解。该项目有两个主要目标：(1)继续开发牢固地基于生物物理学和生物化学的肌肉模型，(2)在严格控制的动物实验中测试和验证该模型。该模型是对A.F.赫胥黎的生物物理跨桥收缩理论的数学近似。神经肌肉控制系统的一个最重要的元素--它的执行器骨骼肌--的当前模型往往是相当粗糙的粘弹性类比，与关于肌肉如何工作的现代生物学概念只有最微妙的联系。在这个项目中，将继续开发一个骨骼肌纤维的状态变量模型，作为对A.F.赫胥黎介绍的那种生物物理跨桥模型的直接数学近似。这个模型被称为肌肉的分布力矩模型，因为它强调了肌动蛋白-肌球蛋白键分布函数的力矩的重要作用。这些力矩有宏观的解释，如肌肉僵硬、力和弹性能量。因此，这个模型在肌肉的宏观行为和被认为在分子水平上运行的收缩机制之间建立了直接的联系，这一点特别有意义。该项目是与西北大学的赫克曼共同努力的(资助金编号为9419528)。***

9318631 Zahalak The research proposed in this application concerns a quantitative understanding of the dynamics of skeletal muscle. The project has two major objectives: (1) to continue the development of a model of muscle firmly based on biophysics and biochemistry, and (2) to test and validate the model in carefully controlled animal experiments. The model is a mathematical approximation to A.F. Huxley's biophysical cross-bridge theory of contraction. Current models for a most important element of the neuromuscular control system-its actuator, skeletal muscle-have tended to be rather crude viscoelastic analogies with only the most tenuous connection to modern biological concepts about how the muscle works. A state-variable model of a skeletal muscle fiber as a direct mathematical approximation to biophysical cross-bridge models of the type introduced by A.F. Huxley will continue to be developed in this project. This model is call the Distributed-Moment Model of muscle because it emphasizes the important role of the moments of the actin-myosin bond-distribution function. These moments have macroscopic interpretations as muscle stiffness, force, and elastic energy. Thus it is of particular significance that this model establishes a direct connection between the macroscopic behavior of muscle and contractile mechanisms believed to be operating at the molecular level. The project is a joint effort with Heckman at Northwestern University (grant number 9419528). ***