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

Washington State University, Pullman WA

Investigators

Abstract

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.