Elucidating multi-scale contractile and morphological mechanisms that empower skeletal muscle to be a better motor

阐明使骨骼肌成为更好运动能力的多尺度收缩和形态机制

• 批准号: 2312925
• 负责人: Bertrand Tanner
• 金额: $ 89.07万
• 依托单位: Washington State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-10-01 至 2026-09-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2312925&HistoricalAwards=false
• 关键词: Elucidating; multi; scale; contractile; morphological

Daily activities, such as walking or lifting a bag of groceries, rely upon a complicated set of interactions between the muscle, tendon, and skeletal systems. There are still many details that scientists do not understand about the underlying mechanisms that enable movement. One challenge in better understanding these mechanisms arises from the vast number of inter-connected processes that contribute to musculoskeletal function. The proposed research aims to identify and characterize two biological mechanisms of coupling, between the molecular and tissue levels, within this system. Computer models and mechanical-feedback experiments will be used to test whether dynamic responses between muscles and their tendons lead to greater force and power output as muscles contract. Addressing two specific mechanisms herein will lay the groundwork to diversify this approach and cross-examine other, complementary mechanisms that enable movement in future studies. Expected outcomes will advance knowledge and better define how skeletal muscles generate force and power output, and how the muscle-tendon interface helps produce movement. Findings will influence fields ranging from rehabilitation and sports medicine to the design of robotic systems and comparative biomechanics. Outreach activities will expand the inclusion of Native American populations in STEM fields and increase the diversity of the technical workforce. These latter activities will be guided by the local Tribal Nations and focus on musculoskeletal health, with events on campus and mentoring undergraduates to perform research in the lab. Formal assessment plans will help evaluate the depth of scientific impact, outreach, and engagement with the students.Many mechanisms may augment the function of skeletal muscle, as a motor, to produce a rich variety of movements. This includes processes underlying muscle work and power output, and effects of tendons, musculoskeletal geometry, and inertia of the body. These mechanisms are intrinsically coupled, where behavior of one component influences behavior of another component, creating a multi-scale feedback system. The impacts of these mechanisms on movement are poorly understood because studying different mechanisms in isolation neglects the coupling between them. The proposed study aims to elucidate the relative importance of two coupled mechanisms that likely increase muscle work production: i) length-dependent cross-bridge kinetics, and ii) variable muscle gearing. Research will investigate individual and combined effects of these mechanisms via expanded computational models, and a newly developed hybrid experimental-simulation feedback system that couples muscle mechanics, muscle morphology, tendon properties, and inertia. These new approaches will enable manipulation of biophysical, biochemical, and mechanical mechanisms of muscle contraction across multiple scales. The findings will advance understanding of the relative contribution of these two mechanisms on skeletal muscle’s ability to better generate work and produce organismal movement.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.

日常活动，如走路或提起一袋杂货，依赖于肌肉，肌腱和骨骼系统之间的一系列复杂的相互作用。科学家们仍然不了解使运动的潜在机制的许多细节。更好地理解这些机制的一个挑战来自于大量有助于肌肉骨骼功能的相互关联的过程。拟议的研究旨在确定和表征该系统中分子和组织水平之间的两种生物耦合机制。计算机模型和机械反馈实验将用于测试肌肉和肌腱之间的动态反应是否会导致肌肉收缩时更大的力量和功率输出。在此讨论两个具体机制将为使这一方法多样化奠定基础，并交叉审查其他补充机制，使未来的研究能够取得进展。预期的结果将推进知识，更好地定义骨骼肌如何产生力量和功率输出，以及肌肉-肌腱界面如何帮助产生运动。研究结果将影响从康复和运动医学到机器人系统设计和比较生物力学等领域。外联活动将扩大美洲原住民在STEM领域的参与，并增加技术劳动力的多样性。后者的活动将由当地部落民族指导，重点是肌肉骨骼健康，校园活动和指导本科生在实验室进行研究。正式的评估计划将有助于评估科学影响的深度，外展和与学生的互动。许多机制可以增强骨骼肌的功能，作为一种运动，产生丰富多样的运动。这包括肌肉工作和功率输出的基础过程，以及肌腱，肌肉骨骼几何形状和身体惯性的影响。这些机制是内在耦合的，其中一个组件的行为影响另一个组件的行为，从而创建多尺度反馈系统。这些机制对运动的影响知之甚少，因为孤立地研究不同的机制忽略了它们之间的耦合。拟议的研究旨在阐明可能增加肌肉做功的两种耦合机制的相对重要性：i）长度依赖性跨桥动力学，以及ii）可变肌肉传动装置。研究将通过扩展的计算模型和新开发的混合实验-模拟反馈系统来研究这些机制的单独和综合影响，该系统将肌肉力学，肌肉形态，肌腱特性和惯性结合起来。这些新方法将能够在多个尺度上操纵肌肉收缩的生物物理、生物化学和机械机制。这一发现将促进对这两种机制对骨骼肌更好地做功和产生机体运动能力的相对贡献的理解。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。