The determinants of maximum muscle performance and the implications for its variation across muscles, ontogenies, environments, and body plans

Skeletal muscle is the biological motor, converting chemical energy into the dazzling array of animal movements observed in nature. Over the last 100 years, the field of muscle physiology has developed a rich understanding of muscle performance based largely on the contractile proteins, actin and myosin. However, empirical findings suggest that muscle performance cannot be explained solely in terms of actin and myosin. And simulation studies suggest that internal resistive forces arising from structural properties of muscle such as mass, viscosity and elasticity, external resistive forces arising from body mass, and the gearing of the system, may limit muscle acceleration and so velocity. This suggests that muscle performance is an emergent property arising from actin and myosin, structural properties of muscle, body mass, environmental forces, and gearing. Here we develop and use 2 methods to empirically determine whether these internal and external resistive forces and their gearing meaningfully affect muscle and organismal performance. In aim 1 we vary muscle recruitment to decouple actin-myosin forces from the structural properties of muscle and compare the effect of recruitment across pairs of muscles or conditions that vary in either viscosity, elasticity, or mass to determine the effect of these internal resistive forces on muscle performance. In aim 2 we expand on an existing muscle virtual reality system which integrates a physics simulator with an isolated muscle to enable determination of the effect of gravitational and inertial forces, and gearing, on muscle performance across simulated body sizes and limb geometries. This systematic, empirical investigation of the effect of internal and external resistive forces and their gearing on muscle velocity has major implications for our understanding of the determinants of muscle and organismal performance, and so its constraints, variation, and adaptation. This project focuses on terrestrial locomotion, but explores a fundamental principle of muscle-driven movements equally applicable to any movement in any environment. Our current theories of muscle contraction attribute shortening velocity entirely to actin-myosin interactions. However, if muscle viscosity is an important determinant of muscle performance, the greater viscosity of cold muscles may reduce velocity. If muscle elasticity is an important determinant of muscle performance, then velocity will be reduced in ageing and pathological muscles which have increased stiffnesses. If the mass is an important determinant of muscle velocity, then it will be reduced in larger muscles and animals. And if the gearing is an important determinant of muscle performance, the high gearing observed in larger animals may not only increase force but also velocity. Hence, understanding the role of internal and external resistive force and gearing in muscle performance is critical to understanding, interpreting and predicting performance across muscles, ontogenies, environments and body sizes. This improved understanding will provide unique insights into long known but poorly understood phenomena such as the scaling of maximum speed, and complicates the interpretation of locomotor specialization of extant and extinct species based only on skeletal morphology. The proposed study expands on an existing muscle virtual reality system using the open-source physics simulator MuJoCo. We will make this resource available to the biomechanics community so providing a powerful, accessible open-source tool for study of muscle-driven movements. The findings of these studies will be used to inform and validate existing myosin-based musculoskeletal simulations widely used in human and clinical applications, beginning with a symposium and workshop that brings together experts in these areas. And this project will provide extensive training opportunities for undergraduate and graduate students, and post-doctoral researchers in individual labs, through collaboration across the 3 labs, and by integration with existing mentoring and career development programs at UCR, CSUF and UCI. Thus, this project will provide technical benefits to the fields of muscle physiology and comparative, human, and clinical biomechanics, and will contribute to training the next generation of researchers.