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

肌肉质量：肌肉建模和模拟中关键但缺失的组成部分

• 批准号: 10586547
• 负责人: Andrew A Biewener
• 金额: $ 48.99万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-06 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10586547
• 关键词: Activities of Daily Living; Address; Adult; Affect; Animals; Architecture; Area; Behavior; Cerebral Palsy; Characteristics; Child; Clinic; Computer Models; Computers; Data; Disease; Elderly; Exhibits; Fatty acid glycerol esters; Fiber; Gait; Goals; Goat; Growth; Health; Human; Human Activities; Human body; In Situ; In Vitro; Intervention; Longevity; Measures; Mechanics; Modeling; Motion; Motor; Movement; Mus; Muscle; Muscle Fibers; Muscle function; Musculoskeletal; Output; Performance; Persons; Physiological; Property; Publishing; Rattus; Recording of previous events; Research; Running; Shapes; Speed; Tendon structure; Testing; Time; Walking; Work; design; improved; in silico; intercalation; kinematics; models and simulation; muscle form; predictive modeling; rehabilitation strategy; simulation; virtual

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.

肌肉骨骼模拟可量化运动过程中的肌肉力量，并经过严格的经验验证 研究具有改善许多人终生流动性的巨大潜力。然而，目前的肌肉骨骼 模拟通常会受到生理上不准确的肌肉模型的影响，这阻碍了对肌肉模型的可靠预测 随时间变化的肌肉力量，限制了它们在临床中的质量和实用性。尽管其他因素 已知会阻碍肌肉模型的准确性，我们假设根本原因是组织的缺失 肌肉骨骼模型中的质量。非活动肌肉质量与日常生活的次最大活动最相关 (ADL)，显着限制肌肉缩短速度、做功和功率输出。我们的试点数据表明 不活跃的质量、纤维排列和肌肉膨胀之间发生显着的相互作用，从根本上来说 影响肌肉的收缩特性。该提案将量化肌肉大小和不活动质量对运动的影响 原位抽搐时间、峰值缩短速度以及对小鼠、大鼠不同大小和形状的肌肉的作用， 和山羊（1000 倍尺寸范围）；以及与这些肌肉的小纤维束相比。我们的 动物研究的综合收缩特性结果将为质量敏感肌肉的设计提供信息 模型，这些模型将被纳入计算高效的肌肉骨骼模拟（编号 19,600 次人体运动周期（比之前发表的研究多 104 次），以测试肌肉大小、 不活跃的质量、形状和纤维类型会影响整个生命周期中执行 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 平行纤维动物肌肉的研究；测试 [H1a] 由于次最大，更多不活跃的肌肉质量 激活（即 ADL），产生较慢的肌肉缩短并减少特定质量的工作输出，并且 [H1b] 与纤维束相比，对于较大的肌肉和整个肌肉，这些影响将会加剧。 SA2 解决了纤维排列如何与非活动质量相互作用以影响不同大小羽状体的工作 小鼠、大鼠和山羊肌肉，与平行纤维肌 (SA1) 进行比较，检验假设 [H2] 羽状肌对次最大激活引起的不活动肌肉质量不太敏感，并且 与平行纤维肌肉相比，其缩短速度和做功的减少幅度较小。 SA3 通过模拟解决肌肉大小如何影响 ADL 和步态动力学的激活和功能 通过计算将质量增强的肌肉模型构建到 OpenSim 模拟中 有效的直接搭配来比较不同尺寸的人体肌肉骨骼模型（1 - 1/1000 身体 大量的）。这些模拟将检验以下假设：[H3a] 较大的肌肉用较低的肌肉产生较少的工作 比较小的肌肉效率更高，并且[H3b]随着质量的增加而减少的工作对于快速运动来说更为明显 肌肉。因此，在肌肉骨骼模拟中结合肌肉质量和纤维类型可以预测 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。