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.

在运动过程中量化肌肉力量的肌肉骨骼模拟，在经验中严格验证 研究有很大的潜力，可以改善许多人的终身流动性。但是，当前的肌肉骨骼 模拟通常遭受身体上不准确的肌肉模型，这阻碍了可靠的预测 时变的肌肉力量，限制了其在诊所中的质量和实用性。虽然其他因素是 已知以阻碍肌肉模型的准确性，我们假设一个基本原因是没有组织 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最大活动最相关 （ADL），显着限制肌肉缩短速度，工作和功率输出。我们的飞行员数据显示 非活动质量，纤维排列和肌肉隆起之间发生了显着相互作用，从根本上讲 影响肌肉收缩特性。该建议将量化肌肉大小和非活动质量对 原位抽搐时间，峰值缩短速度，并在小鼠，大鼠，大鼠，大小和形状的肌肉中工作 和山羊（1000倍范围）；与这些肌肉的小纤维束相比。我们的 动物研究的全面收缩财产结果将为大敏感肌肉的设计提供信息 模型将纳入计算高效的肌肉骨骼模拟（编号） 人类运动的19,600个周期比以前发表的研究多104个，以测试肌肉大小， 非活性质量，形状和纤维类型会影响在整个生命周期内执行ADL和步态所需的激活。 SA1解决了肌肉不活动质量和大小如何通过原位和体外影响收缩性能 平行纤维动物肌肉的研究；测试[H1A]由于次临时而导致更多无活性肌肉质量 激活（即ADL）会产生较慢的肌肉缩短和减少质量特异性工作输出，[H1B] 与纤维束相比，对于较大的肌肉和整个肌肉，这些作用将加剧。 SA2解决了纤维布置如何与非活动质量相互作用，以影响不同尺寸的漆皮的工作 小鼠，大鼠和山羊肌肉，与平行纤维肌肉（SA1）进行比较，检验假设[H2] 甲酸盐的肌肉对由次最大激活和 与平行型肌肉相比，缩短速度和工作的减少较小。 SA3解决了肌肉大小如何通过模拟影响ADL和步态动力学的激活和功能 人类运动将质量增强的肌肉模型构建为使用计算的Opensim模拟 有效的直接搭配比较不同尺寸尺寸的人肌肉骨骼模型（1-1/1000尸体 大量的）。这些模拟将检验假设：[H3A]较大的肌肉产生的工作较少，较低 效率比较小的肌肉，[H3B]降低质量增加的工作更为明显 肌肉。因此，将肌肉质量和纤维类型纳入肌肉骨骼模拟中 更依赖慢肌纤维的激活以实现步态和日常生活的活动。