Altered mechanical properties of titin immunoglobulin domain 27 in the presence of calcium
Altered mechanical properties of titin immunoglobulin domain 27 in the presence of calcium
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DOI：
10.1007/s00249-012-0875-8
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发表时间：
2013-04-01
影响因子：
2
通讯作者：
Herzog, Walter
中科院分区：
文献类型：
--
作者：
DuVall, Michael M.;Gifford, Jessica L.;Herzog, Walter
以连接蛋白为基础的被动力调节机制是适应不同肌肉拉伸条件的重要生理机制。在拉伸时，titin表现得像一个弹簧，能够根据肌肉生物化学的变化来调节其弹性反应。一种这样的机制是钙依赖的titin结构域的硬化，使弹簧固有地更耐拉伸。这种短暂的titin-calcium相互作用可能在肌肉中起到保护作用，当肌肉伸长到很大的长度时，它可以阻止昂贵的选择区域展开。为了验证这一想法，荧光光谱显示了钙对titin免疫球蛋白结构域27 （I27）微环境的影响。此外，通过原子力显微镜，通过拉伸8个连接的titin I27结构域直至它们展开，来评估被动力的钙依赖性调节。当在钙的存在下拉伸时，I27均聚物链变得稳定，并显示出三个新特性：(1)展开结构域需要更高的拉伸力；(2)以持续长度（PL）衡量的刚度增加；(3)相邻I27结构域之间的峰间距离增加。此外，力和PL的峰阶依赖性变得明显，反映了用这种方法表征聚合物动态展开历史的重要性。总之，这种新的titin - ig -钙相互作用可能有助于稳定I27结构域，允许titin以钙依赖的方式调节拉伸肌肉中的被动力。
Titin (connectin) based passive force regulation has been an important physiological mechanism to adjust to varying muscle stretch conditions. Upon stretch, titin behaves as a spring capable of modulating its elastic response in accordance with changes in muscle biochemistry. One such mechanism has been the calcium-dependent stiffening of titin domains that renders the spring inherently more resistant to stretch. This transient titin-calcium interaction may serve a protective function in muscle, which could preclude costly unfolding of select domains when muscles elongate to great lengths. To test this idea, fluorescence spectroscopy was performed revealing a change in the microenvironment of the investigated immunoglobulin domain 27 (I27) of titin with calcium. Additionally, an atomic force microscope was used to evaluate the calcium-dependent regulation of passive force by stretching eight linked titin I27 domains until they unfolded. When stretching in the presence of calcium, the I27 homopolymer chain became stabilized, displaying three novel properties: (1) higher stretching forces were needed to unfold the domains, (2) the stiffness, measured as a persistence length (PL), increased and (3) the peak-to-peak distance between adjacent I27 domains increased. Furthermore, a peak order dependence became apparent for both force and PL, reflecting the importance of characterizing the dynamic unfolding history of a polymer with this approach. Together, this novel titin Ig-calcium interaction may serve to stabilize the I27 domain permitting titin to tune passive force within stretched muscle in a calcium-dependent manner.