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，量化运动过程中的肌肉力量，在经验中得到严格验证 研究，有很大的潜力，以改善许多人的终身流动性。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， 随时间变化的肌肉力量，这限制了它们的质量和在临床上的有用性。虽然其他因素 已知阻碍肌肉模型的准确性，我们假设一个根本原因是缺乏组织 肌肉骨骼模型中的质量。非活动性肌肉质量与日常生活的次最大活动最相关 (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， 非活性物质、纤维排列和肌肉膨胀之间发生显著的相互作用， 影响肌肉收缩特性。这项建议将量化肌肉大小和非活动质量对 对小鼠、大鼠 和山羊（1000倍大小范围）;以及与来自这些肌肉的小纤维束相比。我们 来自动物研究的全面收缩性能结果将为质量敏感肌肉的设计提供信息 模型，这将被纳入计算效率高的肌肉骨骼模拟（编号 19，600个周期-比先前发表的研究多104个），以测试肌肉大小， 非活动的质量、形状和纤维类型影响在整个寿命期间执行ADL和步态所需的激活。 SA 1通过原位和体外研究，阐述了肌肉非活动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[H1 a]，由于次最大 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，这些影响将加剧。 SA 2解决了纤维排列如何与非活性物质相互作用，以影响不同大小羽状体的工作。 小鼠、大鼠和山羊肌肉，与平行纤维肌肉（SA 1）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， 与平行纤维肌肉相比， SA 3通过模拟解决了肌肉大小如何影响ADL和步态动力学的激活和功能 人体运动的模型，将质量增强的肌肉模型构建到OpenSim模拟中， 有效的直接配置，以比较不同大小比例的人体肌肉骨骼模型（1 - 1/1000身体 质量）。这些模拟将测试假设：[H3 a]较大的肌肉产生较少的工作， 效率比较小的肌肉，和[H3 b]，减少工作与增加质量是更明显的快速 肌肉.因此，在肌肉骨骼模拟中模拟肌肉质量和纤维类型可以预测 更多地依赖于较慢肌肉纤维的激活来实现步态和日常生活活动。