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Locomotion is essential for vertebrate survival. Forces required for movement are generated by skeletal muscle. Skeletal muscle shortening and/or force generation occur via parallel sliding of two protein filaments: actin and myosin. This is driven by the cycling of cross-bridges, whose unitary nanometer length change and picoNewton force output are fueled by conversion of chemical energy, stored in the form of adenosine triphosphate, into a change in myosin protein configuration. The range of force and length changes of a muscle is determined by factors such as muscle cross section, fiber angle, tendon attachment, and lever geometry, but also by the metabolic pathways available for adenosine triphosphate synthesis and by enzymes involved in cross-bridge cycling. In addition, muscle mechanical activity is affected by the extent of actin and myosin filament overlap. Force output can be graded by selective recruitment of motor units and/or by variation of force output from individual units. The cost of locomotion is subject to species differences and is affected by the environment and form of movement, with an energy efficiency of up to 0.4. Overall, design principles of vertebrate skeletal muscle may serve as an interesting reference point for novel actuator technologies.