Department of Biological Sciences, Columbia University, New York, NY 10027, USA; email:
Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University Medical Center, New York, NY 10032, USA.
Annu Rev Physiol. 2018 Feb 10;80:327-351. doi: 10.1146/annurev-physiol-021317-121254.
Single-molecule atomic force microscopy and magnetic tweezers experiments have demonstrated that titin immunoglobulin (Ig) domains are capable of folding against a pulling force, generating mechanical work that exceeds that produced by a myosin motor. We hypothesize that upon muscle activation, formation of actomyosin cross bridges reduces the force on titin, causing entropic recoil of the titin polymer and triggering the folding of the titin Ig domains. In the physiological force range of 4-15 pN under which titin operates in muscle, the folding contraction of a single Ig domain can generate 200% of the work of entropic recoil and occurs at forces that exceed the maximum stalling force of single myosin motors. Thus, titin operates like a mechanical battery, storing elastic energy efficiently by unfolding Ig domains and delivering the charge back by folding when the motors are activated during a contraction. We advance the hypothesis that titin folding and myosin activation act as inextricable partners during muscle contraction.
单分子原子力显微镜和磁镊实验已经证明，肌联蛋白免疫球蛋白（Ig）结构域能够在拉力的作用下折叠，产生的机械功超过肌球蛋白马达产生的机械功。我们假设，在肌肉激活时，肌球蛋白交联桥的形成降低了肌联蛋白上的力，导致肌联蛋白聚合物的熵回弹，并触发肌联蛋白 Ig 结构域的折叠。在肌联蛋白在肌肉中工作的生理力范围 4-15pN 内，单个 Ig 结构域的折叠收缩可以产生 200%的熵回弹功，并且发生在超过单个肌球蛋白马达最大失速力的力下。因此，肌联蛋白的作用类似于机械电池，通过展开 Ig 结构域有效地储存弹性能量，并在收缩期间马达被激活时通过折叠返回电荷。我们提出假设，在肌肉收缩过程中，肌联蛋白折叠和肌球蛋白激活是不可分割的伙伴。
