Meeting Abstract
Muscle models that incorporate activation, force-length, and force-velocity properties of muscle perform poorly at predicting forces in work loop experiments. One reason for this failure is that many models do not account for force enhancement with stretch or force depression with shortening. The winding filament hypothesis seeks to explain these phenomena. The hypothesis suggests that titin binds to thin filaments in muscle sarcomeres upon calcium influx, and that myosin cross-bridges wind titin onto thin filaments during force development. In the model, myosin cross-bridges are represented as a damped contractile element with a force-length relationship. Thin filaments are represented by a pulley with radius R, around which a damped titin spring is wrapped. The pulley system is in series with a tendon spring. Activation of the contractile element rotates the pulley, stretching and storing elastic energy in the titin spring. External forces applied to the muscle also extend or shorten the titin and tendon springs. The model uses first order differential equations that describe its kinematics and kinetics, but does not currently include equations to convert muscle stimulation into muscle activation. Incorporation of a stimulation-dependent activation function that approximates calcium dynamics improves the accuracy of WFH model predictions of force development, tetanus, and relaxation during isometric stimulation of mouse soleus muscles at frequencies ranging from 15hz-90hz. This method also improves force predictions of mouse soleus undergoing variable length changes under stimulation at 15hz-75hz. Converting ex vivo stimulation to changes in activation by this method may assist with the development of dynamic muscle models and allow for more accurate predictions of muscle force during work loop experiments.
