Investigating Passive Muscle Mechanics With Biaxial Stretch.

INTRODUCTION: The passive stiffness of skeletal muscle can drastically affect muscle function in vivo, such as the case for fibrotic tissue or patients with cerebral palsy. The two constituents of skeletal muscle that dominate passive stiffness are the intracellular protein titin and the collagenous extracellular matrix (ECM). However, efforts to correlate stiffness and measurements of specific muscle constituents have been mixed, and thus the complete mechanisms for changes to muscle stiffness remain unknown. We hypothesize that biaxial stretch can provide an improved approach to evaluating passive muscle stiffness. METHODS: We performed planar biaxial materials testing of passively stretched skeletal muscle and identified three previously published datasets of uniaxial materials testing. We developed and employed a constitutive model of passive skeletal muscle that includes aligned muscle fibers and dispersed ECM collagen fibers with a bimodal von Mises distribution. Parametric modeling studies and fits to experimental data (both biaxial and previously published) were completed. RESULTS: Biaxial data exhibited differences in time dependent behavior based on orientation (p < 0.0001), suggesting different mechanisms supporting load in the direction of muscle fibers (longitudinal) and in the perpendicular (transverse) directions. Model parametric studies and fits to experimental data exhibited the robustness of the model (<20% error) and how differences in tissue stiffness may not be observed in uniaxial longitudinal stretch, but are apparent in biaxial stretch. CONCLUSION: This work presents novel materials testing data of passively stretched skeletal muscle and use of constitutive modeling and finite element analysis to explore the interaction between stiffness, constituent variability, and applied deformation in passive skeletal muscle. The results highlight the importance of biaxial stretch in evaluating muscle stiffness and in further considering the role of ECM collagen in modulating passive muscle stiffness.