Unfolding of titin domains explains the viscoelastic behavior of skeletal myofibrils
Unfolding of titin domains explains the viscoelastic behavior of skeletal myofibrils
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DOI：
10.1016/s0006-3495(01)76116-4
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发表时间：
2001-03-01
影响因子：
3.4
通讯作者：
Linke, WA
中科院分区：
文献类型：
--
作者：
Minajeva, A;Kulke, M;Linke, WA
巨肌蛋白肌联蛋白的弹性部分含有许多免疫球蛋白样结构域，单分子力学研究表明，这些结构域在拉伸释放后会展开和重折叠。在这里，我们问是否IG域和/或其他肌联蛋白区域的机械性能可以负责非活化的腹肌节的粘弹性，特别是应力松弛和力滞后。我们发现，孤立的腰大肌肌原纤维响应拉伸保持协议的特征力衰减，变得更加明显的拉伸到2.6妈妈以上的肌节长度。力衰减是很容易再现的Monte Carlo模拟考虑到动力学的Ig-域展开和蠕虫状链模型的熵弹性用于描述肌联蛋白的弹性行为。模型表明，力衰减是可以解释的，只有非常少量的IG域每个肌联蛋白分子的解折叠。模拟还预测，肌联蛋白中的一个独特序列，PEVK结构域，可能会在肌节延伸过程中发生微小的结构变化。肌原纤维进行1赫兹周期的拉伸释放表现出明显的滞后，持续在重复测量。快速拉伸释放协议，其中变量暂停后推出的释放，揭示了一个双指数的滞后恢复的时间过程。恢复的速率常数相比，以及与重折叠率的Ig样或纤连蛋白样结构域测量单蛋白质的机械分析。这些研究结果表明，在肌节，肌联蛋白的免疫球蛋白域区域可能作为熵弹簧能够调整其轮廓长度响应拉伸。
The elastic section of the giant muscle protein titin contains many immunoglobulin-like domains, which have been shown by single-molecule mechanical studies to unfold and refold upon stretch-release. Here we asked whether the mechanical properties of Ig domains and/or other titin regions could be responsible for the viscoelasticity of nonactivated skeletal-muscle sarcomeres, particularly for stress relaxation and force hysteresis. We show that isolated psoas myofibrils respond to a stretch-hold protocol with a characteristic force decay that becomes more pronounced following stretch to above 2.6-mum sarcomere length. The force decay was readily reproducible by a Monte Carlo simulation taking into account both the kinetics of Ig-domain unfolding and the worm-like-chain model of entropic elasticity used to describe titin's elastic behavior. The modeling indicated that the force decay is explainable by the unfolding of only a very small number of Ig domains-per titin molecule. The simulation also predicted that a unique sequence in titin, the PEVK domain, may undergo minor structural changes during sarcomere extension. Myofibrils subjected to 1-Hz cycles of stretch-release exhibited distinct hysteresis that persisted during repetitive measurements. Quick stretch-release protocols, in which variable pauses were introduced after the release, revealed a two-exponential time course of hysteresis recovery. The rate constants of recovery compared well with the refolding rates of Ig-like or fibronectin-like domains measured by single-protein mechanical analysis. These findings suggest that in the sarcomere, titin's Ig-domain regions may act as entropic springs capable of adjusting their contour length in response to a stretch.