Estimation of Shear Stress Variation in Extracellular Matrix Caused by Duchenne Muscular Dystrophy

Abstract

Continuous degeneration of muscle tissue, inflammatory processes and fibrosis characterized by a loss of muscle mass, formation of micro-scars, adipose tissue in the muscles and eventual muscle punctures are often signs of muscular dystrophies (dystrophinopathies). These neuromuscular diseases result from genetic mutations of a structural protein called dystrophin. The absence of functional dystrophin leads to the most common and severe form of muscular dystrophy, Duchenne muscular dystrophy (DMD). Typically, within one muscle bundle there are so-called fast and slow muscle fibers that shorten and lengthen at different speeds during muscle contraction. Using the multiscale muscle platform Mexie we evaluated how the lack of dystrophin affects the connective tissue deformation between these two types of muscle fibers. By adjusting the elasticity of extracellular matrix layer, we estimated the magnitude of the shear strain under unloaded and lightly loaded fiber contractions caused by differences in shortening velocities between fast and slow fibers. The simulations showed that without dystrophin large shear strains are generated causing local micro injury and inflammation leading to further muscle degeneration. The multiscale muscle modeling approach presented here could help accelerate understanding of DMD and lead to faster development of new drugs and treatments of patients.