Cross bridges, tendons and titin: evolving roles in muscle mechanics

All fields of science evolve over time as interpretation of the evidence changes with the discovery of new facts, and muscle physiology is no exception. Ideas once thought preposterous may eventually become accepted dogma, as was the case for the sliding filament theory itself. The currently accepted sliding-filament - swinging cross-bridge paradigm views muscles as motors with static isometric force-length and isotonic force-velocity properties that necessarily limit their ability to store and recover viscoelastic energy. These limitations understandably led to the plausible explanation that tendons must be responsible for energy storage and recovery. However, recent advances in technology have enabled investigation of muscle properties in moving humans and other animals, providing significant new data on dynamic muscle function. Bridging the gap between laboratory studies of ex vivo muscle preparations and in vivo muscle mechanics has resulted in a paradigm shift toward the idea that muscles are tunable viscoelastic actuators that can harvest substantial energy from interactions with the environment. Here, we provide a somewhat chronological account of the contentious history of the field of muscle physiology and the evolution of ideas about muscle function, focusing particularly on muscle viscoelastic properties and energy storage. We argue that accumulating data position titin as a length- and activation-dependent viscoelastic element whose properties can be inferred from, and indeed are critical for, in vivo muscle function. We also provide ideas for future directions to stimulate progress in understanding titin's role in dynamic muscle function.