Compliant realignment of binding sites in muscle: Transient behavior and mechanical tuning
Compliant realignment of binding sites in muscle: Transient behavior and mechanical tuning
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DOI：
10.1016/s0006-3495(98)77875-0
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发表时间：
1998-04-01
影响因子：
3.4
通讯作者：
Chase, PB
中科院分区：
文献类型：
--
作者：
Daniel, TL;Trimble, AC;Chase, PB
肌肉中细丝晶格中顺应性的存在引起了人们对如何解释跨桥循环结合部位运动和跨桥之间的耦合背景下的力产生的一些担忧，扰乱了更传统的分析。为了探索这些问题，我们开发了一个空间显式的骨骼肌收缩的机械力化学模型。通过一个简单的三态跨桥循环模型，我们使用蒙特卡罗模拟计算了整个灯丝晶格中的力的瞬时平衡，同时考虑了细丝和粗丝对跨桥力的响应。将这种方法与更传统的质量作用动力学模型(以耦合偏微分方程式的形式)进行比较，后者假定细丝不可伸长。在模拟步长变化和缩短速度变化的过程中，我们还监测了瞬时力的产生、ATP的利用以及跨桥周期的动态。从我们的分析中发现了三个关键的结果：1)随着跨桥力的变化，肌动蛋白结合位点发生了显著的重新排列，2)这种重新排列招募了额外的跨桥结合，以及3)我们预测了与速度和长度瞬变实验结果一致的力学行为。结合位的重排取决于灯丝晶格和跨桥的相对柔度，在这些参数的测量范围内，会产生一个急剧调谐的力产生峰。分子水平上的这种机械调谐是由粗丝变形介导的单个交叉桥之间的机械耦合的结果，以及由此产生的细丝上结合位置的重新排列。
The presence of compliance in the lattice of filaments in muscle raises a number of concerns about how one accounts for force generation in the context of the cross-bridge cycle-binding site motions and coupling between cross-bridges confound more traditional analyses. To explore these issues, we developed a spatially explicit, mechanochemical model of skeletal muscle contraction. With a simple three-state model of the cross-bridge cycle, we used a Monte Carlo simulation to compute the instantaneous balance of forces throughout the filament lattice, accounting for both thin and thick filament distortions in response to cross-bridge forces. This approach is compared to more traditional mass action kinetic models (in the form of coupled partial differential equations) that assume filament inextensibility. We also monitored instantaneous force generation, ATP utilization, and the dynamics of the cross-bridge cycle in simulations of step changes in length and variations in shortening velocity. Three critical results emerge from our analyses: 1) there is a significant realignment of actin-binding sites in response to cross-bridge forces, 2) this realignment recruits additional cross-bridge binding, and 3) we predict mechanical behaviors that are consistent with experimental results for velocity and length transients. Binding site realignment depends on the relative compliance of the filament lattice and cross-bridges, and within the measured range of these parameters, gives rise to a sharply tuned peak for force generation. Such mechanical tuning at the molecular level is the result of mechanical coupling between individual cross-bridges, mediated by thick filament deformations, and the resultant realignment of binding sites on the thin filament.