A strain-dependency of Myosin off-rate must be sensitive to frequency to predict the B-process of sinusoidal analysis.

Muscle force arises as the result of many myosin molecules, each producing a force discrete in magnitude and in time duration. In previous work we have developed a computer model and a mathematical model of many myosin molecules acting as an ensemble and demonstrated that the time duration over which myosin produces force at the molecular level (referred to here as "time-on") gives rise to specific visco-elastic properties at the whole muscle level. That model of the mechanical consequences of myosin-actin interaction predicted well the C-process of small length perturbation analysis and demonstrated that the characteristic frequency 2πc provided a measure of the myosin off-rate, which is equal to the reciprocal of the mean time-on. In this study, we develop a mathematical hypothesis that a strain-dependence of the myosin off-rate at the single molecule level can result in a negative viscous modulus like that observed at low frequencies, i.e., the B-process. We demonstrate here that a simple monotonic strain-dependency of the myosin off-rate cannot account for the observed B-process. However, a frequency-dependent strain-dependency, as may occur when visco-elastic properties of the myosin head are introduced, can explain the observed negative viscous modulus. These findings suggest that visco-elastic properties of myosin constitute the specific molecular mechanisms that underlie the frequency-dependent performance of many oscillatory muscles such as insect flight muscle and mammalian cardiac muscle.