From muscles to motor control: a role for titin in movement

Muscle force adjusts to sudden length changes and allows animals stability during ongoing movement in unpredictable environments. The widely accepted sliding filament and cross bridge theories, based on muscle proteins actin and myosin, are unable to explain how muscle force instantly increases with stretching and decreases with shortening. A third muscle protein, titin, was discovered after the publication of the sliding filament theory and may help us understand muscle force under dynamic conditions. Increased titin stiffness with muscle activation is a potential mechanism behind the instantaneously stiffness with muscle stretching and compliance with shortening. In the first chapter of this doctoral dissertation, I describe the role of muscles in animal movement and how titin may help us understand principles of motor control. The second chapter describes experiments that examine the role of titin in intrinsic muscle properties using the muscular dystrophy with myositis (mdm) mouse with a deletion in titin. I found that when muscles from mdm mice were actively stretched or shortened they were impaired in automatic force adjustments, such as force enhancement and force depression, compared to wild type muscles. The winding filament hypothesis incorporates a role for titin in active muscle force generation and allowed us to develop a muscle model that predicts in vivo muscle forces. Computational muscle models are incorporated into the control of robots, prostheses and exoskeletons to reproduce natural movement. Unlike our muscles, however, engineered approaches to control provide no inherent adaptation to varying environmental conditions. To overcome this, we developed an algorithm based on the winding filament hypothesis and incorporated it into the control software of the BiOM. We tested the bio-inspired controller in two individuals with a transtibial amputation and found that both subjects were able to successfully transition from level walking to stair ascent. By including a role for titin in muscle contraction, we were able to emulate intrinsic muscle force adjustments and provide adaptive biomimetic control for a robotic foot-ankle prosthesis