Institute of Biomedical Engineering, Boğaziçi University, Istanbul, Turkey.
Institute of Biomedical Engineering, Boğaziçi University, Istanbul, Turkey.
J Biomech. 2021 Feb 12;116:110197. doi: 10.1016/j.jbiomech.2020.110197. Epub 2020 Dec 25.
Active state titin's effects have been studied predominantly in sarcomere or muscle fiber segment level and an understanding of its functional effects in the context of a whole muscle, and the mechanism of those is lacking. By representing experimentally observed calcium induced stiffening and actin-titin interaction induced reduced free spring length effects of active state titin in our linked fiber-matrix mesh finite element model, our aim was to study the mechanism of effects and particularly to determine the functionally more effective active state titin model. Isolated EDL muscle of the rat was modeled and three cases were studied: passive state titin (no change in titin constitutive equation in the active state), active state titin-I (constitutive equation involves a higher stiffness in the active state) and active state titin-II (constitutive equation also involves a strain shift coefficient accounting for titin's reduced free spring length). Isometric muscle lengthening was imposed (initial to long length, l = 28.7 mm to 32.7 mm). Compared to passive state titin, (i) active state titin-I and II elevates muscle total (l = 32.7 mm: 14% and 29%, respectively) and active (l = 32.7 mm: 37.5% and 77.4%, respectively) forces, (ii) active state titin-II also shifts muscle's optimum length to a longer length (l = 29.6 mm), (iii) active state titin-I and II limits sarcomere shortening (l = 32.7 mm: up to 10% and 20%, respectively). Such shorter sarcomere effect characterizes active state titin's mechanism of effects. These effects become more pronounced and functionally more effective if not only calcium induced stiffening but also a reduced free spring length of titin is accounted for.
主动状态肌联蛋白的作用主要在肌节或肌纤维段水平进行研究，而对其在整个肌肉中的功能作用及其机制缺乏了解。通过在我们的纤维-基质网格有限元模型中表示实验观察到的钙诱导的僵硬和肌动球蛋白-肌联蛋白相互作用引起的主动状态肌联蛋白的自由弹簧长度减小的影响，我们的目的是研究作用机制，特别是确定功能上更有效的主动状态肌联蛋白模型。对大鼠的腓肠肌进行建模，并研究了三种情况：被动状态肌联蛋白（主动状态下肌联蛋白的本构方程没有变化）、主动状态肌联蛋白-I（本构方程涉及主动状态下更高的刚度）和主动状态肌联蛋白-II（本构方程还涉及应变转移系数，用于说明肌联蛋白的自由弹簧长度减小）。施加等长肌肉伸长（初始长度为 28.7mm 至 32.7mm）。与被动状态肌联蛋白相比，（i）主动状态肌联蛋白-I 和 II 增加了肌肉的总力（l=32.7mm：分别为 14%和 29%）和主动力（l=32.7mm：分别为 37.5%和 77.4%），（ii）主动状态肌联蛋白-II 还将肌肉的最佳长度移至更长的长度（l=29.6mm），（iii）主动状态肌联蛋白-I 和 II 限制肌节缩短（l=32.7mm：分别高达 10%和 20%）。这种较短的肌节效应是主动状态肌联蛋白作用机制的特征。如果不仅考虑钙诱导的僵硬，而且还考虑肌联蛋白自由弹簧长度的减小，这些效应会更加明显，并且在功能上更加有效。
