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

主动弹簧肌肉模型——骨骼肌力学的新唯象模型

基本信息

批准号：
BB/S003762/1
负责人：
Sang-Hoon Yeo
金额：
$ 51.98万
依托单位：
University of Birmingham
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2019
资助国家：
英国
起止时间：
2019 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FS003762%2F1
关键词：
Active spring muscle model new

项目摘要

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.

了解Machina Carnis，即我们的肌肉如何机械地产生运动，是人体运动科学的基础研究问题之一，在许多应用领域也有重要意义，包括物理治疗、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，我们对肌肉的理解基本上变得难以理解。作为一个突出的例子，我们还没有任何模型可以完全解释肌肉在受到外力拉伸时的行为（称为偏心收缩）。一个众所周知的事实是，肌肉在偏心收缩时起着有效的“刹车”作用，在拉伸时主动稳定自己，只消耗少量的代谢能量。众所周知，偏心收缩对肌肉的机械效率有重要的贡献，但现有的肌肉模型对偏心收缩的解释非常有限，很少有人能理性地认识到这一问题，并提出一个具有更广泛解释范围的替代模型。在上层的肌肉骨骼建模研究中，肌肉力学中的这个“难以忽视的真相”尤其被忽视，在这些研究中，简单的肌肉模型是非常受欢迎的，以便有效地模拟大量肌肉的行为。尽管传统肌肉模型在预测肌肉的动态收缩行为（包括偏心收缩）方面存在许多问题，但已有80年历史的hill型肌肉模型仍主要用作肌肉骨骼模拟研究的标准现象学模型。这并不是因为该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型肌肉模型的模型。基于这些原因，本研究旨在建立并验证hill型肌肉模型的有效替代方法。关键的洞察力是最近提出的基于肌收缩理论，统称为活动弹簧模型，显示了阐明许多无法解释的动态肌肉行为的巨大潜力。除了传统的肌动蛋白和肌球蛋白丝之间的滑动丝机制外，活动弹簧模型还强调了连接这些丝的额外的弹簧状丝——肌动蛋白在调节活动肌肉的刚度方面的机械作用。然而，重要的是，所提出的研究并不旨在建立一个纯粹的解释性微观模型，因为力学和参数的简单性往往被牺牲，而是旨在建立一个简单可靠的现象学模型，可以很容易地被上层肌肉骨骼研究人员使用。通过开发这样一个模型，该研究有望弥合肌肉和肌肉骨骼研究之间长达80年的鸿沟。拟议的研究将采取综合方法来实现这一目标。该研究将首先专注于在受控的体外设置下建立单个纤维/肌肉模型。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样刺激模式。在此之后，该模型将在体内人体实验中进一步验证，重点是通过结合新的非侵入性技术来估计工作肌肉的结构和力学变化，预测运动过程中腿部肌肉的力学。作为影响的途径，模型和仿真代码将通过开放源代码肌肉项目网站OpenMuscle.org向普通肌肉骨骼建模者/研究人员开放。