Abstract
Mice are often used as animal models of various human neuromuscular diseases, and analysis of these models often requires detailed gait analysis. However, little is known of the dynamics of the mouse musculoskeletal system during locomotion. In this study, we used computer optimization procedures to create a simulation of trotting in a mouse, using a previously developed mouse hindlimb musculoskeletal model in conjunction with new experimental data, allowing muscle forces, activation patterns, and levels of mechanical work to be estimated. Analyzing musculotendon unit (MTU) mechanical work throughout the stride allowed a deeper understanding of their respective functions, with the rectus femoris MTU dominating the generation of positive and negative mechanical work during the swing and stance phases. This analysis also tested previous functional inferences of the mouse hindlimb made from anatomical data alone, such as the existence of a proximo-distal gradient of muscle function, thought to reflect adaptations for energy-efficient locomotion. The results do not strongly support the presence of this gradient within the mouse musculoskeletal system, particularly given relatively high negative net work output from the ankle plantarflexor MTUs, although more detailed simulations could test this further. This modeling analysis lays a foundation for future studies of the control of vertebrate movement through the development of neuromechanical simulations.
Highlights
Many of the neuromuscular diseases that are studied using mice as a model organism, such as Duchenne Muscular Dystrophy (DMD) and Amyotrophic Lateral Sclerosis (ALS), are known to severely affect gait
Vertical ground reaction forces (GRFs) (Figure 2D) on average peaked at 0.21 N (120% of body mass) at 55.1% of stance
Optimization procedures allowed individual muscle activation patterns and levels of mechanical work to be analyzed in detail for a single trotting stride
Summary
Many of the neuromuscular diseases that are studied using mice as a model organism, such as Duchenne Muscular Dystrophy (DMD) and Amyotrophic Lateral Sclerosis (ALS), are known to severely affect gait. While detailed computerized biomechanical simulations have been used to estimate muscle forces and activations in human gait in many studies (Pandy, 2001; Zajac et al, 2003; Roberts and Belliveau, 2005; Liu et al, 2006; Lee and Piazza, 2009; McGowan et al, 2009; Miller et al, 2012; Steele et al, 2012; van der Krogt et al, 2012; Modenese et al, 2013; Pires et al, 2014), few similar studies into animal gait exist (Full and Ahn, 1995; Kargo et al, 2002; Merritt et al, 2008; Aoi et al, 2013; Sellers et al, 2013, 2017; Rankin et al, 2016) Factors such as joint moments, individual muscle forces, muscle contraction dynamics and muscle activation patterns during locomotion can be difficult or, depending on the subject, impossible to measure in a purely experimental context. Musculoskeletal modeling is an opportunity to gain insight into muscle functions within the mouse musculoskeletal system, which could be used to inform new and/or improved animal models of neuromuscular diseases
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