Investigating Passive Muscle Mechanics With Biaxial Stretch

Abstract

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.

It's more than the amount that counts: implications of collagen organization on passive muscle tissue properties revealed with micromechanical models and experiments

“…This highlights the need to characterize the behaviour of biological tissues, which are highly variable between animals, during multiple distinct loading states, as well as the advantage of our coupled framework to minimize errors from experimental measurements alone. Previous studies characterized anisotropic muscle tissue properties through uniaxial testing in multiple directions [44–46], or biaxial testing with equivalent along- and cross-muscle fibre lengthening strains [15,47]. Our model predictions reflected trends measured in diaphragm muscle tissue, with higher cross- relative to along-muscle fibre stiffness under uniaxial loading [8–10] and higher cross-muscle fibre stiffness in mdx relative to WT models during equibiaixal lengthening [15].…”

Hill-type models of skeletal muscle and neuromuscular actuators: a systematic review

“…This is an important limitation, as the FL relationship is for example known to be piecewise linear at the sarcomere scale but to be smoother with larger plateau (Hatze, 1980) and more slowly decreasing descending limb beyond optimal fibre length at larger scales (Herzog, Walter et al, 2015), a multiscale difference sometimes debated (Winters, Taylor M. et al, 2011; Moo et al, 2020). Also, the curvature of the FV relationship decreases with higher scales (compare (Ranatunga, 1982; McDonald et al, 1994; Roots et al, 2007) for works on rat skinned fibres, bundles of fibres, and whole muscles), while the Young’s modulus in the exponential stress-strain relationship of the PEE nonlinearly increases from the fibre to the muscle scale (Ward et al, 2020), with dominant contributions to the total passive force of the titin structures and of the extracellular matrix at the fibre and muscle scales respectively (Prado et al, 2005; Ward et al, 2020; Wheatley, 2020). Consequently, the multiscale Hill-type modelling must be correctly applied and commented to maintain credible descriptions of the muscle physiology and dynamics.…”

Fibronectin: Molecular Structure, Fibrillar Structure and Mechanochemical Signaling

“…On a whole-tissue level, biaxial tensile testing on excised specimens can be used to quantify overall ECM mechanical properties, and these properties can be correlated with ECM composition, ECM fiber alignment, and ECM morphology [ 114 , 115 ]. However, these assays fail to specifically probe the contribution of FN fibrils.…”