Titin's role in muscle mechanics from molecules to movement

Recent studies demonstrate that N2A titin binds strongly to actin in vitro in the presence of calcium. This interaction should decrease titin length, increase titin stiffness, and produce a dependence of mechanical behavior on length at the time of activation. These properties are absent in skeletal mdm muscles, a mutation that produces a 83-amino acid deletion in N2A titin. Recent muscle models that incorporate these titin properties perform well at predicting in vivo muscle force in guinea fowl leg muscles during running on a treadmill with barrier perturbations, and also provide adaptive control of a robotic foot-ankle prosthesis during level walking and stair ascent. Experimental observations and model simulations reveal previously overlooked relationships between muscle length, velocity, and force that help to explain why muscle activation is weakly correlated with muscle force production.