Nature of PEVK-titin elasticity in skeletal muscle
Nature of PEVK-titin elasticity in skeletal muscle
复制标题
DOI：
10.1073/pnas.95.14.8052
复制
发表时间：
1998-07-07
影响因子：
11.1
通讯作者：
Kolmerer, B
中科院分区：
文献类型：
--
作者：
Linke, WA;Ivemeyer, M;Kolmerer, B
在巨大的titin分子中有一个独特的序列，PEVK结构域，被认为在拉伸过程中对放松骨骼肌的被动力发展有很大的贡献。为了探索PEVK弹性的本质，我们使用titin特异性抗体对大鼠腰肌肌原纤维PEVK区域的两端进行染色，并通过免疫荧光和免疫电镜结合分离的肌原纤维力学来确定该区域的力-伸关系，然后试图将结果与最近的聚合物弹性模型拟合。在肌节长度超过2.4 μ m处，PEVK片段明显延长，并在大约3.5 μ m处达到其估计的轮廓长度。在免疫荧光标记的肌节中，在超过3 μ m处反复拉伸和释放，可以很容易地看到可逆的PEVK延长。在接近轮廓长度的延伸处，计算出每个titin分子的平均力约为45 pN，试图用标准的蠕虫状熵弹性链模型拟合PEVK片段的力-延伸曲线，仅在低至中等延伸时才成功。与此相反，实验数据也可以用包含焓弹性的改进虫链模型正确地拟合在高扩展处。焓的贡献很可能来自于静电硬化，这可以从肌原纤维硬度的离子强度依赖性中得到证明；在高拉伸时，疏水效应也可能变得相关。因此，在生理肌肉长度上，PEVK区域不像纯熵弹簧那样起作用。相反，PEVK弹性可能具有熵和焓两种来源，可由聚合物的持久长度和拉伸模量表征。
A unique sequence within the giant titin molecule, the PEVK domain, has been suggested to greatly contribute to passive force development of relaxed skeletal muscle during stretch. To explore the nature of PEVK elasticity, we used titin-specific antibodies to stain both ends of the PEVK region in rat psoas myofibrils and determined the region's force-extension relation by combining immunofluorescence and immunoelectron microscopy with isolated myofibril mechanics, We then tried to fit the results with recent models of polymer elasticity. The PEVK segment elongated substantially at sarcomere lengths above 2.4 mu m and reached its estimated contour length at approximate to 3.5 mu m. In immunofluorescently labeled sarcomeres stretched and released repeatedly above 3 mu m, reversible PEVK lengthening could be readily visualized. At extensions near the contour length, the average force per titin molecule was calculated to be approximate to 45 pN, Attempts to fit the force-extension curve of the PEVK segment with a standard wormlike chain model of entropic elasticity were successful only for low to moderate extensions. In contrast, the experimental data also could be correctly fitted at high extensions with a modified wormlike chain model that incorporates enthalpic elasticity. Enthalpic contributions are likely to arise from electrostatic stiffening, as evidenced by the ionic-strength dependency of titin-based myofibril stiffness; at high stretch, hydrophobic effects also might become relevant. Thus, at physiological muscle lengths, the PEVK region does not function as a pure entropic spring. Rather, PEVK elasticity may have both entropic and enthalpic origins characterizable by a polymer persistence length and a stretch modulus.