Muscle Mass: a Critical but Missing Component in Muscle Modeling and Simulation

肌肉骨骼模拟，量化运动中的肌肉力量，在经验中得到严格验证 学习，对改善许多人的终身行动能力有很大潜力。然而，目前的肌肉骨骼 模拟通常受到生理上不准确的肌肉模型的影响，这些模型阻碍了可靠的预测 时变的肌肉力量，这限制了它们的质量和在临床上的有效性。尽管其他因素包括 已知的阻碍肌肉模型准确性的因素，我们假设根本原因是缺乏组织 肌肉骨骼模型中的质量。不活跃的肌肉质量与日常生活的次极量活动最相关 (ADL)，显著限制肌肉缩短速度、功和功率输出。我们的试点数据显示， 在不活跃的质量、纤维排列和肌肉膨胀之间发生显著的相互作用，这从根本上 会影响肌肉的收缩特性。这项建议将量化肌肉大小和不活跃质量对 小鼠、大鼠、大鼠不同大小、不同形状肌肉的原位抽动时间、最大收缩速度和功 和山羊(1000倍大小的范围)；以及与这些肌肉的小纤维束相比。我们的 来自动物研究的综合收缩性能结果将为质量敏感型肌肉的设计提供参考 模型，这些模型将被合并到计算效率高的肌肉骨骼模拟(编号 19,600个周期--比之前发表的研究多104个周期)，以测试肌肉大小， 不活跃的质量、形状和纤维类型影响在整个寿命中执行ADL和步态所需的激活。 SA1通过原位和体外研究肌肉不活跃的质量和大小如何影响收缩性能 对平行纤维的动物肌肉的研究；测试[H1a]由于次最大值导致的更多不活跃的肌肉质量 激活(即ADL)，产生较慢的肌肉缩短和减少的质量比功输出，[H1B] 与纤维束相比，对于较大的肌肉和整个肌肉来说，这些影响将加剧。 SA2阐述了纤维排列如何与非活性物质相互作用，从而影响不同大小的羽叶植物的作功 小鼠、大鼠和山羊肌肉，与平行纤维肌肉(SA1)进行比较，验证假设[H2] 羽状肌对亚极量激活引起的不活跃的肌肉质量不那么敏感 与平行纤维肌肉相比，在缩短速度和做功方面表现出较小的减少。 SA3通过模拟解决了肌肉大小如何影响ADL和步态动力学中的活动和功能 通过计算将质量增强的肌肉模型构建到OpenSim模拟中 高效的直接搭配来比较不同大小的人体肌肉骨骼模型(1-1/1000个体 质量)。这些模拟将检验假设：[H3a]较大的肌肉与较低的肌肉产生的功较少 与较小的肌肉相比，效率更高，[H3B]随着质量的增加而减少的功在FAST中更加明显 肌肉。因此，在肌肉骨骼模拟中结合肌肉质量和纤维类型是可以预测的 更多地依赖较慢的肌肉纤维的激活来实现步态和日常生活活动。

Musculoskeletal simulations that quantify muscle forces during movements, rigorously validated in empirical studies, have great potential to improve life-long mobility for many persons. However, current musculoskeletal simulations generally suffer from physiologically inaccurate muscle models that hinder reliable prediction of time-varying muscle force, which limits their quality and usefulness in the clinic. Although other factors are known to hinder muscle model accuracy, we hypothesize that a fundamental cause is the absence of tissue mass in musculoskeletal models. Inactive muscle mass is most relevant to submaximal activities of daily living (ADL), significantly limiting muscle shortening velocity, work, and power output. Our pilot data show that significant interactions occur between inactive mass, fiber arrangement, and muscle bulging that fundamentally affect muscle contractile properties. This proposal will quantify the effects of muscle size and inactive mass on in situ twitch time, peak shortening velocity, and work for different-sized and -shaped muscles in mice, rats, and goats (1000-fold size range); as well as in comparison to small fiber bundles from these muscles. Our comprehensive contractile property results from animal studies will inform the design of mass-sensitive muscle models, which will be incorporated into computationally efficient musculoskeletal simulations (numbering 19,600 cycles – 104 more than studies previously published) of human movement to test how muscle size, inactive mass, shape, and fiber type affect the activations needed to execute ADL and gait across the lifespan. SA1 addresses how muscle inactive mass and size affect contractile performance via in situ and in vitro studies of parallel-fibered animal muscles; testing [H1a] that more inactive muscle mass, due to submaximal activation (i.e., ADL), yields slower muscle shortening and reduced mass-specific work output, and [H1b] that these effects will be exacerbated for larger muscles and for whole muscles, as compared to fiber bundles. SA2 addresses how fiber arrangement interacts with inactive mass to influence work in different-sized pennate mouse, rat, and goat muscles, with comparisons to parallel-fibered muscles (SA1), testing the hypothesis [H2] that pennate muscles will be less sensitive to inactive muscle mass caused by submaximal activation and show smaller reductions in shortening velocity and work, compared to parallel-fibered muscles. SA3 addresses how muscle size affects activation and function across ADL and gait dynamics via simulations of human movement that build mass-enhanced muscle models into OpenSim simulations with computationally efficient direct collocation to compare differently size-scaled human musculoskeletal models (1 - 1/1000th body mass). These simulations will test the hypotheses: [H3a] that larger muscles generate less work with lower efficiency than smaller muscles, and [H3b] that reduced work with increased mass is more pronounced for fast muscle. Incorporating muscle mass and fiber-types in musculoskeletal simulations therefore stands to predict greater reliance on activations of slower muscle fibers to achieve gait and activities of daily living.