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

日常活动，如走路或提一袋杂货，依赖于肌肉、肌腱和骨骼系统之间复杂的相互作用。关于运动的潜在机制，科学家们仍有许多细节不了解。更好地理解这些机制的一个挑战来自于大量相互关联的过程，这些过程有助于肌肉骨骼功能。提出的研究旨在确定和表征该系统中分子和组织水平之间耦合的两种生物学机制。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在肌肉收缩时产生更大的力量和能量输出。在此解决两个特定的机制将奠定基础，使这种方法多样化，并交叉检验其他互补机制，使运动在未来的研究。预期的结果将促进知识的发展，并更好地定义骨骼肌如何产生力量和能量输出，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。外展活动将扩大美国土著人口在STEM领域的包容性，并增加技术劳动力的多样性。后一项活动将由当地部落国家指导，重点关注肌肉骨骼健康，在校园举办活动，并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、外延和与学生的接触。许多机制可以增强骨骼肌的功能，作为一个马达，产生丰富多样的运动。这包括潜在的肌肉工作和能量输出过程，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，创建一个多尺度反馈系统。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。该研究旨在阐明可能增加肌肉功产出的两种耦合机制的相对重要性：i)长度相关的过桥动力学，ii)可变肌肉传动。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个和组合效应，该系统将肌肉力学、肌肉形态、肌腱特性和惯性结合起来。这些新方法将使跨多个尺度的肌肉收缩的生物物理、生化和机械机制的操作成为可能。这些发现将促进对这两种机制对骨骼肌更好地产生工作和产生有机运动能力的相对贡献的理解。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.