Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy.
Center for Biosystems Dynamics Research, RIKEN, Suita 565-0874, Japan.
Int J Mol Sci. 2023 Mar 27;24(7):6265. doi: 10.3390/ijms24076265.
Contraction in striated muscle is classically described as regulated by calcium-mediated structural changes in the actin-containing thin filaments, which release the binding sites for the interaction with myosin motors to produce force. In this view, myosin motors, arranged in the thick filaments, are basically always ready to interact with the thin filaments, which ultimately regulate the contraction. However, a new "dual-filament" activation paradigm is emerging, where both filaments must be activated to generate force. Growing evidence from the literature shows that the thick filament activation has a role on the striated muscle fine regulation, and its impairment is associated with severe pathologies. This review is focused on the proposed mechanical feedback that activates the inactive motors depending on the level of tension generated by the active ones, the so-called mechanosensing mechanism. Since the main muscle function is to generate mechanical work, the implications on muscle mechanics will be highlighted, showing: (i) how non-mechanical modulation of the thick filament activation influences the contraction, (ii) how the contraction influences the activation of the thick filament and (iii) how muscle, through the mechanical modulation of the thick filament activation, can regulate its own mechanics. This description highlights the crucial role of the emerging bi-directional feedback on muscle mechanical performance.
横纹肌的收缩通常被描述为通过钙介导的肌动蛋白丝中含有的结构变化来调节，这种变化释放了与肌球蛋白马达相互作用的结合位点，从而产生力。在这种观点中，排列在粗丝中的肌球蛋白马达基本上随时准备与细丝相互作用，从而最终调节收缩。然而，一种新的“双丝”激活范例正在出现，其中两根细丝都必须被激活才能产生力。越来越多的文献证据表明，粗丝的激活对横纹肌的精细调节起着作用，其功能障碍与严重的病理有关。这篇综述主要集中在提出的机械反馈机制上，该机制根据活性肌丝产生的张力水平激活非活性肌丝，即所谓的机械感知机制。由于肌肉的主要功能是产生机械功，因此将重点强调其对肌肉力学的影响，展示：（i）粗丝激活的非机械调节如何影响收缩，（ii）收缩如何影响粗丝的激活，以及（iii）肌肉如何通过粗丝激活的机械调节来调节自身的力学特性。这种描述突出了新兴的双向反馈对肌肉力学性能的关键作用。
