Project Summary All movements involve dynamic interactions between passive elastic structures and muscle contractile elements, but our understanding of the consequences of this interaction for both normal and pathological muscle function is limited. Our long-term goal is to define the mechanical influence of elastic elements on muscle force production and gait. This project aims to understand how the mechanical interaction between internal muscle elastic elements, fluid pressure, and contractile elements define muscle force, speed and power output. Previous work shows that this interaction is highly three-dimensional and significantly influences muscle performance. A dominant paradigm of muscle force production as a one-dimensional process determined primarily by contractile element properties has limited our understanding. The project aims to use a combination of modeling and experiment to test novel hypotheses about how multi-scale, three- dimensional interactions influence muscle mechanical output. A combination of direct measurement of contractile behavior of muscles in different animal systems and physical models is used to test mechanistic hypotheses about how structures at multiple scales interact to influence mechanical output. The specific aims of the project are: 1) to test the hypothesis that fluid forces contribute to muscle force output, 2) to determine whether stiffened connective tissue in older muscle reduces force and work output, 3) to test the hypothesis that muscle fluid volume influences passive muscle stiffness, and 4) to test the hypothesis that dynamic changes in muscle architecture provide a mechanism for intramuscular elastic energy storage and recovery. In most cases the mechanistic link between structural pathologies in muscle and functional deficits is poorly developed. We will test novel hypothesized mechanisms for how changes in extracellular matrix and muscle fluid content can alter muscle mechanical output with the aim of determining structure-function relationships that may underpin functional deficits in a range of conditions, including dystrophies, cerebral palsy, aging, and secondary to stroke and spinal cord injury. These models will inform the design of rehabilitative strategies and interventions to improve muscle-tendon function. An improved understanding of how muscle elastic elements influence the mechanical behavior of healthy muscle-tendon units may also aid in the design of prosthetic devices.