Muscle Mass: a Critical but Missing Component in Muscle Modeling and Simulation

Musculoskeletal simulations that quantify muscle forces during movements, rigorously validated in empirical
studies, have great potential to improve life-long mobility for many persons. However, current musculoskeletal
simulations generally suffer from physiologically inaccurate muscle models that hinder reliable prediction of
time-varying muscle force, which limits their quality and usefulness in the clinic. Although other factors are
known to hinder muscle model accuracy, we hypothesize that a fundamental cause is the absence of tissue
mass in musculoskeletal models. Inactive muscle mass is most relevant to submaximal activities of daily living
(ADL), significantly limiting muscle shortening velocity, work, and power output. Our pilot data show that
significant interactions occur between inactive mass, fiber arrangement, and muscle bulging that fundamentally
affect muscle contractile properties. This proposal will quantify the effects of muscle size and inactive mass on
in situ twitch time, peak shortening velocity, and work for different-sized and -shaped muscles in mice, rats,
and goats (1000-fold size range); as well as in comparison to small fiber bundles from these muscles. Our
comprehensive contractile property results from animal studies will inform the design of mass-sensitive muscle
models, which will be incorporated into computationally efficient musculoskeletal simulations (numbering
19,600 cycles – 104 more than studies previously published) of human movement to test how muscle size,
inactive mass, shape, and fiber type affect the activations needed to execute ADL and gait across the lifespan.
SA1 addresses how muscle inactive mass and size affect contractile performance via in situ and in vitro
studies of parallel-fibered animal muscles; testing [H1a] that more inactive muscle mass, due to submaximal
activation (i.e., ADL), yields slower muscle shortening and reduced mass-specific work output, and [H1b] that
these effects will be exacerbated for larger muscles and for whole muscles, as compared to fiber bundles.
SA2 addresses how fiber arrangement interacts with inactive mass to influence work in different-sized pennate
mouse, rat, and goat muscles, with comparisons to parallel-fibered muscles (SA1), testing the hypothesis [H2]
that pennate muscles will be less sensitive to inactive muscle mass caused by submaximal activation and
show smaller reductions in shortening velocity and work, compared to parallel-fibered muscles.
SA3 addresses how muscle size affects activation and function across ADL and gait dynamics via simulations
of human movement that build mass-enhanced muscle models into OpenSim simulations with computationally
efficient direct collocation to compare differently size-scaled human musculoskeletal models (1 - 1/1000th body
mass). These simulations will test the hypotheses: [H3a] that larger muscles generate less work with lower
efficiency than smaller muscles, and [H3b] that reduced work with increased mass is more pronounced for fast
muscle. Incorporating muscle mass and fiber-types in musculoskeletal simulations therefore stands to predict
greater reliance on activations of slower muscle fibers to achieve gait and activities of daily living.

Grant Number: 5R01AR080797-03
NIH Institute/Center: NIH
Principal Investigator: Andrew Biewener