Department of Kinesiology and Physical Education, McGill University, Montreal, QC, Canada, H2W 1S4.
Department of Physics, Willamette University, Salem, OR 97301.
Proc Natl Acad Sci U S A. 2017 Aug 15;114(33):8794-8799. doi: 10.1073/pnas.1700615114. Epub 2017 Aug 1.
The sarcomere is the smallest functional unit of myofibrils in striated muscles. Sarcomeres are connected in series through a network of elastic and structural proteins. During myofibril activation, sarcomeres develop forces that are regulated through complex dynamics among their structures. The mechanisms that regulate intersarcomere dynamics are unclear, which limits our understanding of fundamental muscle features. Such dynamics are associated with the loss in forces caused by mechanical instability encountered in muscle diseases and cardiomyopathy and may underlie potential target treatments for such conditions. In this study, we developed a microfluidic perfusion system to control one sarcomere within a myofibril, while measuring the individual behavior of all sarcomeres. We found that the force from one sarcomere leads to adjustments of adjacent sarcomeres in a mechanism that is dependent on the sarcomere length and the myofibril stiffness. We concluded that the cooperative work of the contractile and the elastic elements within a myofibril rules the intersarcomere dynamics, with important consequences for muscle contraction.
肌节是横纹肌中肌原纤维的最小功能单位。肌节通过弹性和结构蛋白网络串联在一起。在肌纤维激活过程中，肌节产生的力通过其结构之间的复杂动力学进行调节。调节肌节间动力学的机制尚不清楚，这限制了我们对基本肌肉特征的理解。这种动力学与肌肉疾病和心肌病中遇到的机械不稳定性导致的力丧失有关，并且可能为这些病症的潜在靶向治疗提供依据。在这项研究中，我们开发了一种微流控灌注系统，以控制肌原纤维内的一个肌节，同时测量所有肌节的个体行为。我们发现，一个肌节产生的力会导致相邻肌节的调整，这种机制依赖于肌节长度和肌纤维的硬度。我们的结论是，肌原纤维内的收缩和弹性元件的协同工作决定了肌节间的动力学，这对肌肉收缩有重要影响。
