为什么运动能锻炼肌肉：Titin机械传感控制负荷下的骨骼肌生长
Why exercise builds muscles: Titin mechanosensing controls skeletal muscle growth under load
摘要：
肌肉感觉内部产生的和外部施加的力，在不同的时间尺度上以协调的层次方式对这些力做出反应。肌肉的基本单位的中心，肌节M带，被完美地放置以感知肌肉所承受的不同类型的负荷。特别是，肌联蛋白的激酶结构域（TK）位于M带是一个已知的候选人的机械信号。在这里，我们开发了定量的数学模型，描述了动力学TK为基础的机械敏感信号，并预测营养变化的运动和康复制度。首先，我们建立了TK构象变化的动力学模型：开放，磷酸化，信号传导和自抑制。我们发现，TK打开作为一个亚稳态mechanosensitive开关，这自然会产生一个更大的信号后，高负荷的阻力运动比同样精力昂贵的耐力努力。接下来，为了使模型稳定，给出连贯的预测，特别是运动方案开始后的滞后，我们必须考虑磷酸盐（由ATP携带）的相关动力学，以及蛋白质合成速率对肌纤维大小的非线性依赖性。我们认为，后者的效果可能发生通过空间位阻核糖体扩散通过筛状肌丝晶格。完整的模型产生一个稳态的解决方案（稳态）的肌肉横截面积和张力，和一个定量合理的肥大反应的培训以及萎缩后，延长减少紧张。
英文摘要：
Muscles sense internally generated and externally applied forces, responding to these in a coordinated hierarchical manner at different time scales. The center of the basic unit of the muscle, the sarcomeric M-band, is perfectly placed to sense the different types of load to which the muscle is subjected. In particular, the kinase domain (TK) of titin located at the M-band is a known candidate for mechanical signaling. Here, we develop the quantitative mathematical model that describes the kinetics of TK-based mechanosensitive signaling, and predicts trophic changes in response to exercise and rehabilitation regimes. First, we build the kinetic model for TK conformational changes under force: opening, phosphorylation, signaling and autoinhibition. We find that TK opens as a metastable mechanosensitive switch, which naturally produces a much greater signal after high-load resistance exercise than an equally energetically costly endurance effort. Next, in order for the model to be stable, give coherent predictions, in particular the lag following the onset of an exercise regime, we have to account for the associated kinetics of phosphate (carried by ATP), and for the non-linear dependence of protein synthesis rates on muscle fibre size. We suggest that the latter effect may occur via the steric inhibition of ribosome diffusion through the sieve-like myofilament lattice. The full model yields a steady-state solution (homeostasis) for muscle cross-sectional area and tension, and a quantitatively plausible hypertrophic response to training as well as atrophy following an extended reduction in tension.
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