Active spring muscle model - a new phenomenological model of skeletal muscle mechanics

了解机械卡尼斯，即我们的肌肉如何机械地产生运动，是人类运动科学的基础研究问题之一，在许多应用领域也具有重要意义，例如，物理治疗、运动/运动科学和类人机器人。尽管几个世纪以来在微观/纳米水平上阐明肌肉收缩的分子机制方面取得了科学成就，但人们会惊讶地发现，当涉及到实际的力量产生时，我们对肌肉的理解变得非常难以捉摸。作为一个突出的例子，我们还没有任何模型来完全解释肌肉在面对外力(称为偏心收缩)时的行为。一个众所周知的事实是，肌肉在偏心收缩时起到了有效的“刹车”作用，在伸展时主动稳定自己，只消耗最少量的新陈代谢能量。众所周知，偏心收缩对肌肉的机械效率有重要贡献，但目前现有的肌肉模型对偏心收缩的解释非常有限，几乎没有人提出合理认识这一问题并开发具有更广泛解释范围的替代模型的努力。在上层肌肉骨骼建模研究中，肌肉力学中的这一“不方便的真理”尤其被忽视，在这些研究中，为了有效地模拟一大群肌肉的行为，简单的肌肉模型是非常受欢迎的。尽管传统的肌肉模型在预测肌肉的动态收缩行为方面存在许多问题，包括偏心收缩，但已有80年历史的Hill-type肌肉模型主要用作肌肉骨骼模拟研究的标准唯象模型。这并不是因为这一领域的研究人员没有意识到它的弱点，而是因为目前还没有替代Hill-type肌肉模型的替代模型，因此，本研究旨在构建并验证一种有效的Hill-type肌肉模型的替代方案。关键的洞察是最近提出的基于Titin的肌肉收缩理论，统称为活动弹簧模型，显示出解释许多无法解释的动态肌肉行为的巨大潜力。除了肌动蛋白和肌球蛋白细丝之间的传统滑动细丝机制外，主动弹簧模型还突出了肌动蛋白的机械作用，肌动蛋白是一种连接这些细丝的额外弹簧状细丝，在调节主动肌肉的僵硬方面发挥着重要作用。然而，重要的是，拟议的研究的目的不是开发一个纯粹解释性的微观模型，其中机械和参数的简单性往往被牺牲，而是旨在开发一个简单可靠的现象学模型，便于上层肌肉骨骼研究人员使用。通过开发这样的模型，这项研究有望弥合肌肉和肌肉骨骼研究之间长达80年的差距。拟议的研究将采取综合方法来实现这一目标。这项研究将首先专注于在受控的体外设置下建立单一纤维/肌肉的模型。为了确保作为通用肌肉力学模型的可靠性，将在各种动态收缩情况下进行严格的验证，包括偏心收缩和自然运动式刺激模式。之后，该模型将在活体人体实验中得到进一步验证，重点是通过结合新的非侵入性技术来预测腿部肌肉在运动过程中的力学行为，这些技术可以估计工作肌肉的结构和力学变化。作为影响的途径，该模型和模拟代码将通过开源肌肉项目网站OpenMuscle.org向普通肌肉骨骼建模师/研究人员开放。

Understanding Machina Carnis, how our muscles mechanically generate movement, is one of the fundamental research questions in human movement science and also has significant implications in many application areas including, to name a few, physiotherapy, sport/exercise science and humanoid robotics. Notwithstanding the scientific achievements over the centuries in elucidating the molecular mechanism of the muscle contraction in micro/nanoscopic levels, one would be surprised to find that our understanding of the muscle becomes substantially elusive when it comes to the actual force production. As a highlighting example, we do not yet have any model that fully explains muscle's behaviour when it is being stretched against an external force (called eccentric contraction). A well-known fact is that the muscle works as an efficient "brake" during eccentric contraction, actively stabilising itself against a stretch consuming a just minimal amount of metabolic energy. Eccentric contraction is known to make a critical contribution to the muscle's mechanical efficiency, but currently existing muscle models offer very limited explanations on eccentric contraction and little effort has been put forward to rationally recognize this issue and to develop an alternative model that has a wider explanatory scope.This "inconvenient truth" in muscle mechanics has been particularly overlooked in the upper-layer, musculoskeletal modelling studies, where simple muscle models are highly preferred in order to efficiently simulate the behaviour a large group of muscles. Despite numerous problems of the conventional muscle models in predicting dynamic contractile behaviour of the muscle, including eccentric contraction, the eighty years old Hill-type muscle model is predominantly used as a standard phenomenological model of the musculoskeletal simulation studies. This is not because the researchers in this area are unaware of its weaknesses, but because there is no alternative model that can yet replace the Hill-type muscle model.For these reasons, the proposed study aims to build and validate an effective alternative to the Hill-type muscle model. The key insight is on the recently proposed titin-based muscle contraction theories, collectively called the active spring model that shows great potential for elucidating many unexplained dynamic muscle behaviours. In addition to the traditional sliding-filament mechanism between the actin and the myosin filament, the active spring model highlights the mechanical role of titin, an additional spring-like filament that connects those filaments, in regulating the stiffness of the active muscle. It is important, however, that the proposed study does not aim to develop a purely explanatory, microscopic model of which the mechanical and parametric simplicity is often sacrificed, but aims to develop a simple and reliable phenomenological model that can be readily used by upper-layer musculoskeletal researchers. By developing such a model, the study is expected to bridge an eighty-years standing gap between muscle and musculoskeletal studies.The proposed study will take an integrative approach to achieve this goal. The study will first focus on building a model of single fiber/muscle under a controlled in vitro setup. To ensure the reliability as a general-purpose muscle mechanics model, rigorous validations will be conducted under various dynamic contractile situations, including eccentric contraction and naturalistic locomotion-like stimulation patterns. After that, the model will be further validated in the in vivo human experiment, focusing on predicting the mechanics of leg muscle during locomotion, by incorporating novel non-invasive techniques that estimate the architectural and mechanical changes of the working muscle. As a pathway to impact, the model and the simulation code will be open to general musculoskeletal modellers/researchers via OpenMuscle.org, an open-source muscle project website.