Heidlauf Thomas, Klotz Thomas, Rode Christian, Altan Ekin, Bleiler Christian, Siebert Tobias, Röhrle Oliver
Institute of Applied Mechanics (CE), Pfaffenwaldring 7, 70569, Stuttgart, Germany.
Institute of Motion Science, Friedrich-Schiller-University, Seidelstr. 20, 07749, Jena, Germany.
Biomech Model Mechanobiol. 2016 Dec;15(6):1423-1437. doi: 10.1007/s10237-016-0772-7. Epub 2016 Mar 3.
Although recent research emphasises the possible role of titin in skeletal muscle force enhancement, this property is commonly ignored in current computational models. This work presents the first biophysically based continuum-mechanical model of skeletal muscle that considers, in addition to actin-myosin interactions, force enhancement based on actin-titin interactions. During activation, titin attaches to actin filaments, which results in a significant reduction in titin's free molecular spring length and therefore results in increased titin forces during a subsequent stretch. The mechanical behaviour of titin is included on the microscopic half-sarcomere level of a multi-scale chemo-electro-mechanical muscle model, which is based on the classic sliding-filament and cross-bridge theories. In addition to titin stress contributions in the muscle fibre direction, the continuum-mechanical constitutive relation accounts for geometrically motivated, titin-induced stresses acting in the muscle's cross-fibre directions. Representative simulations of active stretches under maximal and submaximal activation levels predict realistic magnitudes of force enhancement in fibre direction. For example, stretching the model by 20 % from optimal length increased the isometric force at the target length by about 30 %. Predicted titin-induced stresses in the muscle's cross-fibre directions are rather insignificant. Including the presented development in future continuum-mechanical models of muscle function in dynamic situations will lead to more accurate model predictions during and after lengthening contractions.
尽管最近的研究强调了肌联蛋白在增强骨骼肌力量方面可能发挥的作用，但在当前的计算模型中，这一特性通常被忽略。本文提出了首个基于生物物理的骨骼肌连续介质力学模型，该模型除了考虑肌动蛋白-肌球蛋白相互作用外，还考虑了基于肌动蛋白-肌联蛋白相互作用的力量增强。在激活过程中，肌联蛋白附着于肌动蛋白丝，这导致肌联蛋白的自由分子弹簧长度显著缩短，从而在随后的拉伸过程中使肌联蛋白产生的力量增加。肌联蛋白的力学行为包含在一个多尺度化学-电-机械肌肉模型的微观半肌小节层面，该模型基于经典的滑动丝和横桥理论。除了肌联蛋白在肌纤维方向上的应力贡献外，连续介质力学本构关系还考虑了由几何因素驱动的、肌联蛋白在肌肉横纤维方向上产生的应力。在最大和次最大激活水平下对主动拉伸的代表性模拟预测了纤维方向上力量增强的实际大小。例如，将模型从最佳长度拉伸20%，会使目标长度处的等长力增加约30%。预测的肌联蛋白在肌肉横纤维方向上产生的应力相当小。在未来动态情况下肌肉功能的连续介质力学模型中纳入本文提出的进展，将在延长收缩期间及之后带来更准确的模型预测。
