Mechanical fatigue in repetitively stretched single molecules of titin
Mechanical fatigue in repetitively stretched single molecules of titin
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DOI：
10.1016/s0006-3495(01)76064-x
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发表时间：
2001-02-01
影响因子：
3.4
通讯作者：
Granzier, HL
中科院分区：
文献类型：
--
作者：
Kellermayer, MSZ;Smith, SB;Granzier, HL
松弛的横纹肌细胞在反复拉伸和释放循环时表现出机械性疲劳。为了了解这种机械疲劳的分子基础，对决定肌节弹性的主要决定因素--巨丝状蛋白质Titin的单分子进行了重复拉伸和释放，同时用光钳表征了它们的力响应。在重复的拉伸-释放循环中，Titin在我们称为分子疲劳的过程中被机械地磨损。这一过程的特征是拉力曲线逐渐向增加的端到端长度移动，这表明重复的机械循环增加了Titin的有效轮廓长度。在拉伸半周期的初始部分，分子疲劳只发生在受限的力范围(0-25pN)，而其余的力响应从一个机械循环重复到另一个机械循环。蛋白质折叠模型不能解释基于Titin球状结构域不完全重折叠的分子疲劳。相反，这一过程显然源于不稳定的非特异性键的形成，这些键沿着预先展开的Titin片段将不同的位点连接在一起。由于Titin的分子疲劳发生在生理相关的力范围内，这一过程可能在动态调整肌肉对近期机械扰动的反应方面发挥重要作用。
Relaxed striated muscle cells exhibit mechanical fatigue when exposed to repeated stretch and release cycles. To understand the molecular basis of such mechanical fatigue, single molecules of the giant filamentous protein titin, which is the main determinant of sarcomeric elasticity, were repetitively stretched and released while their force response was characterized with optical tweezers. During repeated stretch-release cycles titin becomes mechanically worn out in a process we call molecular fatigue. The process is characterized by a progressive shift of the stretch-force curve toward increasing end-to-end lengths, indicating that repeated mechanical cycles increase titin's effective contour length. Molecular fatigue occurs only in a restricted force range (0-25 pN) during the initial part of the stretch half-cycle, whereas the rest of the force response is repeated from one mechanical cycle to the other. Protein-folding models fail to explain molecular fatigue on the basis of an incomplete refolding of titin's globular domains. Rather, the process apparently derives from the formation of labile nonspecific bonds cross-linking various sites along a pre-unfolded titin segment. Because titin's molecular fatigue occurs in a physiologically relevant force range, the process may play an important role in dynamically adjusting muscle's response to the recent history of mechanical perturbations.