A spatially explicit nanomechanical model of the half-sarcomere:: Myofilament compliance affects Ca2+-Activation
A spatially explicit nanomechanical model of the half-sarcomere:: Myofilament compliance affects Ca2+-Activation
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DOI：
10.1114/b:abme.0000049039.89173.08
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发表时间：
2004-11-01
影响因子：
3.8
通讯作者：
Daniel, TL
中科院分区：
文献类型：
--
作者：
Chase, PB;Macpherson, JM;Daniel, TL
骨骼肌施加的力是由它所连接的组织的顺应性调节的。肌节的力是由肌丝的顺应性调节的。我们通过构建包括纤维顺应性作为变量的肌肉半肌节的计算模型来检验肌丝顺应性影响肌肉Ca2+调节的假设。生物力学模型由3条肌球蛋白半丝和13条细丝组成。粗丝上肌凝蛋白运动结构域的初始间距和细丝上肌凝蛋白结合位点的初始间距取未拉伸丝中实验测量的值。蒙特卡罗模拟用于确定每个交叉桥的三态周期周围和每个细丝调节单元的两态之间的转换。与早期的双丝模型相比，这种多丝模型显示出更少的最大力“调谐”。值得注意的是，肌丝顺应性调节了Ca2+的表观敏感性和稳态等距力激活的协同性。张力发展动力学的活化依赖性也由丝的顺应性调节。在细丝激活的亚最大水平上，整个肌丝晶格的调谐似乎更为显著。
The force exerted by skeletal muscle is modulated by compliance of tissues to which it is connected. Force of the muscle sarcomere is modulated by compliance of the myofilaments. We tested the hypothesis that myofilament compliance influences Ca2+ regulation of muscle by constructing a computational model of the muscle half sarcomere that includes compliance of the filaments as a variable. The biomechanical model consists of three half-filaments of myosin and 13 thin filaments. Initial spacing of motor domains of myosin on thick filaments and myosin-binding sites on thin filaments was taken to be that measured experimentally in unstrained filaments. Monte-Carlo simulations were used to determine transitions around a three-state cycle for each cross-bridge and between two-states for each thin filament regulatory unit. This multifilament model exhibited less "tuning" of maximum force than an earlier two-filament model. Significantly, both the apparent Ca2+-sensitivity and cooperativity of activation of steady-state isometric force were modulated by myofilament compliance. Activation-dependence of the kinetics of tension development was also modulated by filament compliance. Tuning in the full myofilament lattice appears to be more significant at submaximal levels of thin filament activation.