Airway Smooth Muscle Dynamics are Governed by the Imposed Rate of Strain

Abstract

It is commonly believed that the time scale governing the rheology of airway smooth muscle (ASM) is set by the internal viscosity and elasticity of the muscle. We show here, to the contrary, that this time scale is set by the externally imposed rate of strain.For any fixed strain rate amplitude (SRA), the elastic modulus of the ASM showed a sigmoidal dependence upon frequency. Remarkably, as the SRA was increased over a range spanning almost four decades, sigmoidal response curves demonstrated little change of shape but shifted dramatically to higher frequencies. As such, the time scale of underlying molecular processes is set not by any internal viscosity, elasticity, or any spontaneous internal rate process, but instead is set by the imposed rate of strain. When the muscle is loaded at a small strain-rate, the molecular dynamics are slow; when loaded at a large strain-rate, the dynamics are fast.Using numerical computations, we then assessed the contribution of myosin bridge kinetics to this behavior. In the regime where frequency was the highest, a good agreement between data and computations was obtained; ASM dynamics could, therefore, be attributed to forced acto-myosin crossbridge dynamics. But at the lowest frequencies, the slopes differed dramatically and stiffness values differed by an order of magnitude, exposing a new domain of slow dynamics that cannot be accounted for by acto-myosin interactions.Interestingly, these results unify scale-free dynamics, fluidization, and length adaptation. While this unification is not explained by any traditional physical picture of cell rheology or polymer dynamics, it deepens substantially the analogy between living and inert soft matter, and in doing so, reveals a central role for microstructural fragility.