ERI: A Computational and Experimental Approach to Establishing Multiscale and Multiphasic Structure-Function Mechanisms of Muscle Stiffness

ERI：建立肌肉僵硬多尺度、多相结构功能机制的计算和实验方法

• 批准号: 2301653
• 负责人: Benjamin Wheatley
• 金额: $ 20万
• 依托单位: Bucknell University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2301653&HistoricalAwards=false
• 关键词: ERI; Computational; Experimental; Approach; Establishing

This Engineering Research Initiation (ERI) award supports research that will create a model of muscle behavior at multiple scales. Muscle is responsible for providing the power that is necessary to live our daily lives – walking, communicating, and breathing are all possible thanks to skeletal muscle. However, muscle injury, neuromuscular disease, and other impairments can reduce a person’s mobility and cause significant pain because the muscles are too stiff. This project is to investigate how the stiffness and biology of healthy muscle is different from that of impaired muscle. In particular, it is currently unknown how molecules that compose skeletal muscle contribute to the mechanical properties, particularly to muscle stiffness. The project will investigate how three key parts of skeletal muscle contribute to muscle stiffness – a) muscle cells, b) a web-like tissue called the extracellular matrix, and c) the cellular liquids in muscle. The research team will use experimental testing complemented by computer models to generate data. This data will help scientists and clinicians better to understand what specific mechanisms of a disease change muscle stiffness. The results will contribute to improving treatments for people who suffer from such muscle conditions. This grant also will support educational outreach to mentor a diverse group of undergraduate student researchers and support their professional development in careers in the sciences. This work will establish critical structure-function mechanisms in passive skeletal muscle by leveraging multiscale materials testing and finite element analysis. While changes to muscle stiffness from impairments correlate to measurements such as collagen content and type, predicting the hyperelastic, anisotropic material properties of muscle in vivo is not possible. The research team will perform multi-axial materials testing on individual muscle fibers, muscle tissue, and whole muscle under both tensile and compressive conditions. These experimental data will comprise the most comprehensive set of muscle material properties collected to date and will be used for the calibration and validation of a multiscale, biphasic, homogenized finite element model of muscle tissue that links microstructural form to macro function. This model can then be used in future efforts to study how microstructural changes to muscle tissue alter muscle material properties and thus in vivo function.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该工程研究启动（ERI）奖支持将在多个尺度上创建肌肉行为模型的研究。肌肉负责提供生活日常生活所必需的力量 - 由于骨骼肌肉，步行，交流和呼吸都是可能的。但是，肌肉损伤，神经肌肉疾病和其他损害会减少一个人的活动能力并引起严重的疼痛，因为肌肉太僵硬。该项目是为了研究健康肌肉的刚度和生物学与肌肉受损的僵硬程度不同。特别是，目前尚不清楚组成骨骼肌的分子如何有助于机械性能，尤其是肌肉刚度。该项目将研究骨骼肌的三个关键部分如何促进肌肉刚度 - a）肌肉细胞，b）一种称为细胞外基质的网络样组织，以及c）肌肉中的细胞液体。研究团队将使用计算机模型完成的实验测试来生成数据。这些数据将帮助科学家和临床医生更好地了解疾病的特定机制改变肌肉僵硬。结果将有助于改善患有这种肌肉状况的人的治疗方法。该赠款还将支持教育宣传，以指导一群本科生研究人员的潜水员群体，并支持他们在科学职业中的职业发展。这项工作将通过利用多尺度材料测试和有限元分析来建立被动骨骼肌肉中的关键结构功能机制。虽然肌肉刚度的变化与胶原蛋白含量和类型等测量相关，但可以预测肌肉在体内的超弹性，各向异性物质的特性。研究小组将在张力和压缩条件下对单个肌肉纤维，肌肉组织和整个肌肉进行多轴材料测试。这些实验数据将完成迄今为止收集的最全面的肌肉材料特性，并将用于校准和验证肌肉组织的多尺度，双相，均质化有限元模型，该模型将微结构形式与宏观功能联系起来。然后可以将该模型用于未来的努力，以研究肌肉组织的微观结构变化如何改变肌肉材料的特性，该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响审查标准，通过评估诚实地认为支持了肌肉的任务。