Institute of Mechanics, Lomonosov Moscow University, Moscow, Russia.
Biophys J. 2013 Aug 20;105(4):941-50. doi: 10.1016/j.bpj.2013.06.044.
We present a model of Ca-regulated thin filaments in cardiac muscle where tropomyosin is treated as a continuous elastic chain confined in the closed position on the actin helix by electrostatic forces. The main distinction from previous works is that the intrinsic stress-free helical shape of the tropomyosin chain was taken into account explicitly. This results in the appearance of a new, to our knowledge, tension-like term in the energy functional and the equilibrium equation. The competitive binding of calcium and the mobile segment of troponin-I to troponin-C were described by a simple kinetic scheme. The values of dimensionless model parameters were estimated from published data. A stochastic Monte Carlo simulation of calcium curves has been performed and its results were compared to published data. The model explains the high cooperativity of calcium response of the regulated thin filaments even in the absence of myosin heads. The binding of myosin heads to actin increases the calcium sensitivity while not affecting its cooperativity significantly. When the presence of calcium-insensitive troponin-C was simulated in the model, both calcium sensitivity and cooperativity decreased. All these features were previously observed experimentally.
我们提出了一个钙离子调节的心肌细肌丝模型，其中肌球蛋白轻链被视为一种连续的弹性链，通过静电力限制在肌动蛋白螺旋的关闭位置。与以前的工作的主要区别在于，明确考虑了肌球蛋白轻链的固有无应力螺旋形状。这导致了能量函数和平衡方程中出现了一个新的、据我们所知的张力项。钙和肌球蛋白 I 的可移动片段与肌钙蛋白 C 的竞争结合通过一个简单的动力学模型来描述。无量纲模型参数的值是根据已发表的数据估计的。进行了钙曲线的随机蒙特卡罗模拟，并将其结果与已发表的数据进行了比较。该模型解释了调节细肌丝的钙离子反应的高协同性，即使在没有肌球蛋白头部的情况下也是如此。肌球蛋白头部与肌动蛋白的结合增加了钙离子的敏感性，而对其协同性的影响不大。当模型中模拟存在钙不敏感的肌钙蛋白 C 时，钙离子的敏感性和协同性都降低了。所有这些特征以前都在实验中观察到过。
