Use it or lose it: multiscale skeletal muscle adaptation to mechanical stimuli

Abstract

Skeletal muscle undergoes continuous turnover to adapt to changes in its mechanical environment. Overload increases muscle mass, whereas underload decreases muscle mass. These changes are correlated with, and enabled by, structural alterations across the molecular, subcellular, cellular, tissue, and organ scales. Despite extensive research on muscle adaptation at the individual scales, the interaction of the underlying mechanisms across the scales remains poorly understood. Here we present a thorough review and a broad classification of multiscale muscle adaptation in response to a variety of mechanical stimuli. From this classification, we suggest that a mathematical model for skeletal muscle adaptation should include the four major stimuli, overstretch, understretch, overload, and underload, and the five key players in skeletal muscle adaptation, myosin heavy chain isoform, serial sarcomere number, parallel sarcomere number, pennation angle, and extracellular matrix composition. Including this information in multiscale computational models of muscle will shape our understanding of the interacting mechanisms of skeletal muscle adaptation across the scales. Ultimately, this will allow us to rationalize the design of exercise and rehabilitation programs, and improve the long-term success of interventional treatment in musculoskeletal disease.

Contribution of Neuromuscular Factors to Quadriceps Asymmetry After Anterior Cruciate Ligament Reconstruction

“…27À29, 35 A limitation of our work is that we collected isokinetic torque at 608/s, which is a speed known to be influenced by both fast-twitch and slow-twitch fiber types. 28 However, given that we used maximum isokinetic torque to compute asymmetries between limbs, it seems highly plausible that interlimb morphologic differences in isokinetic torque were being regulated by a shift in muscle phenotype from fast-twitch to slow-twitch fibers in the involved limb.…”

Agent-based computational model investigates muscle-specific responses to disuse-induced atrophy

“…These computational models have shown, for example, that diminished muscle size greatly influences strength and mobility (30,63). Models that describe the adaptive response of muscle tissue to modified (75,79) and diminished mechanical loading (74) have been developed. However, these previous models of muscle adaptation have been based on phenomenological equations that describe measurements of tissue responses to alterations in the mechanical environment and therefore are unable to capture and study the effects of molecular signals and cellular behaviors on muscle tissue adaptation.…”

Biomimicry, Biofabrication, and Biohybrid Systems: The Emergence and Evolution of Biological Design

“…Similar studies have also investigated the effect of mechanical loading on other tissue types, including skeletal muscle, which is well known to adaptively respond to "exercise" stimulation. [93] Interestingly, other forms of controlled external stimulation, such as fluid flow, biochemical signals, and electrical signals, have also been shown to have hypertrophic effects on engineered muscle tissue in vitro. [94,95] These studies showcase the ability of biofabricated tissues to serve as platforms for studying the underlying mechanisms of adaptive functional response in living systems.…”