Nonlinear myofilament regulatory processes affect frequency-dependent muscle fiber stiffness

Abstract

To investigate the role of nonlinear myofilament regulatory processes in sarcomeric mechanodynamics, a model of myofilament kinetic processes, including thin filament on-off kinetics and crossbridge cycling kinetics with interactions within and between kinetic processes, was built to predict sarcomeric stiffness dynamics. Linear decomposition of this highly nonlinear model resulted in the identification of distinct contributions by kinetics of recruitment and by kinetics of distortion to the complex stiffness of the sarcomere. Further, it was established that nonlinear kinetic processes, such as those associated with cooperative neighbor interactions or length-dependent crossbridge attachment, contributed unique features to the stiffness spectrum through their effect on recruitment. Myofilament model-derived sarcomeric stiffness reproduces experimentally measured sarcomeric stiffness with remarkable fidelity. Consequently, characteristic features of the experimentally determined stiffness spectrum become interpretable in terms of the underlying contractile mechanisms that are responsible for specific dynamic behaviors.