One of the primary functions of skeletal muscle is to generate force. Physiological and biomechanical experiments have demonstrated that actin-myosin interaction is responsible for force generation. In order to make movements and perform locomotion, force generated by the activation of muscle fibers has to be transmitted to bony skeleton of the body though tendon. A first step of the force transmission process is to allow force to cross the cellular membrane of the muscle cell. Two pathways have been identified for force transmission: longitudinal (myotendinous), and lateral (myofascial) pathways. Transmitting forces from myofibrils to the tendon laterally involves several anatomical structures, including the myofibrils, the extracellular matrix (ECM), and the lateral linkages between myofibrils and the ECM. Despite some observational evidence for the existence of the lateral transmission of force, the exact mechanisms of lateral transmission and how age-related changes in the structural and mechanical properties of the muscle, tendon and ECM affect it are not well understood. Age-related (young vs. old) structural changes are well document and include changes in collagen content, organization, cross-links, fiber diameter, and the thickness of the ECM. We hypothesize that these age-related changes in the structural properties of the ECM will directly effect the mechanical properties and more important, the lateral transmission of force, and thus be a significant mechanism associated with aging-muscle disability syndromes. The objective of this study is to test this hypothesis by examining the effect of aging on the structure and function of the ECM, and to determine how these changes affect the lateral transmission of force. We will experimentally measure the effect of aging (young vs. old) on the structural and mechanical properties of the ECM of skeletal muscle of the rats. Experiments will be performed to assess the effect of aging on lateral transmission of force. A mathematical mechanical model will be used to determine the mechanisms of role of lateral transmission of force, and the role of ECM. To validate the model, we will compare the results from the experimental measurement and model. Parametric studies using the model will be performed to assess factors that will affect lateral transmission of force, including the structural and mechanical properties of the muscle fibers and the ECM, as well as the interactions between the muscle fibers and the ECM. Successful completion of this proposal will provide new clinical information for the treatment, rehabilitation and training strategies for the elderly, individual's with muscular dystrophy, muscle trauma, and injury and disease associated with ECM abnormities, such as polymyositis and sclerosis

Public Health Relevance

The objective of this study is to examine the effect of aging on the structure and function of the ECM, and to determine how these changes affect the lateral transmission of force. Successful completion of this proposal will provide new clinical information for the treatment, rehabilitation and training strategies for the elderly, individual's with muscular dystrophy, muscle trauma, and injury and disease associated with ECM abnormities, such as polymyositis and sclerosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Research Grants (R03)
Project #
5R03AR059225-03
Application #
8213756
Study Section
Special Emphasis Panel (ZAR1-MLB-G (M1))
Program Officer
Boyce, Amanda T
Project Start
2010-05-01
Project End
2014-01-31
Budget Start
2012-02-01
Budget End
2014-01-31
Support Year
3
Fiscal Year
2012
Total Cost
$71,641
Indirect Cost
$23,641
Name
Cornell University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Zhang, Chi; Gao, Yingxin (2014) Effects of aging on the lateral transmission of force in rat skeletal muscle. J Biomech 47:944-8
Zhang, Chi; Gao, Yingxin (2014) The role of transmembrane proteins on force transmission in skeletal muscle. J Biomech 47:3232-6