Search bioRxiv⌕ Search

bioRxiv · 10.64898/2026.06.03.729794

Predictive Neuromechanical Simulation Explains Gait Biomechanics in Obesity

Abstract

Individuals with obesity exhibit gait adaptations including reduced early-stance knee flexion, altered muscle coordination, slower preferred walking speeds, and shorter step lengths. Although these features are well documented, the mechanisms by which obesity-related physiological changes produce these patterns and influence knee joint loading relevant to osteoarthritis (OA) remain unclear. This study used predictive neuromechanical simulation to examine how musculoskeletal changes and movement objectives interact to generate obesity-associated gait patterns and tibiofemoral loading. Predictive simulations were performed using a reflex-based neuromechanical walking model. A baseline non-obese model (1.8 m, 80 kg) was modified to represent obesity-related changes in segment mass distribution and muscle strength (1.8 m, 140 kg), including more apple-like and more pear-like body mass distributions. Control parameters were optimized to generate stable walking while minimizing muscle effort and tibiofemoral joint loading. Objective weightings were identified by matching simulated knee kinematics to experimental observations at a typical walking speed. Using the selected weightings, we compared joint kinematics, kinetics, and muscle activations, and simulations were performed across walking speeds to evaluate optimal walking speed, step length, muscle effort, and knee loading. The baseline model best matched reference knee kinematics using a muscle-effort objective alone, whereas the obese model required a combined objective penalizing both muscle effort and knee loading. This formulation reproduced key gait features, including reduced early-stance knee flexion, reduced vastii activation with increased plantarflexor activation, slower optimal walking speeds, and shorter step lengths. Variations in body mass distribution produced moderate but consistent effects on gait mechanics relative to larger effects of increased body mass. Obesity-related changes in body mass and muscle strength alone did not reproduce observed gait patterns, but incorporating an objective that penalizes knee loading generated multiple characteristic features. Predictive neuromechanical simulation provides a framework for identifying candidate mechanisms linking obesity, gait biomechanics, and knee joint loading. Author SummaryUnderstanding how and why obesity alters gait is a complex biomechanical problem involving multiple interacting factors including increased segmental mass, altered inertial properties, and reduced relative muscle strength. These factors interact in ways that are difficult to isolate through experimental observation alone. Here, we used computer simulations to examine how musculoskeletal changes and movement objectives interact to generate obesity-associated gait patterns and knee loading. We found that physiological changes alone did not reproduce observed gait features, whereas incorporating an objective that penalizes knee loading generated multiple characteristic features simultaneously, including reduced early-stance knee flexion, altered muscle coordination, slower optimal walking speeds, and shorter step lengths. These findings suggest that obesity-associated gait reflects coordination strategies that regulate knee loading under increased body mass.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Choi, C. W., Ton, V., Gill, S. V., Song, S.. 2026-06-08. Predictive Neuromechanical Simulation Explains Gait Biomechanics in Obesity. https://doi.org/10.64898/2026.06.03.729794

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

The impacts of exogenous noise on stochastic disease dynamics

Much of the literature and intuition associated with mathematical epidemiology is driven by deterministic models, which are a reasonable assumption when the population size is large. Stochastic models, especially individual based models, are however considered vital when dealing with small population sizes, especially at times of invasion or extinction. The overwhelming majority of these models (both deterministic and stochastic) assume that the underlying parameters are fixed (or follow a regular seasonal pattern). Here, we consider an analytic framework for dealing with randomly varying parameters through the use of stochastic differential equations - thereby capturing the action of external noisy processes such as weather. In particular, we focus on when the transmission rate, {beta}, varies as the solution to a Cox-Ingersoll-Ross Model, such that {beta} is gamma distributed with autocorrelation. We consider the impact of this parameter variation on a stochastic version of the Susceptible-Infected-Recovered model, and for this 'double-stochastic' model show through simulation and analytical results that exogenous noise increases the impact of stochasticity, potentially leading to more early extinctions, wider variations in the number of cases at equilibrium, but that early growth rate can be faster or slower depending on the precise parameters.

systems biology↗

Site-resolved spatial and structural interactome of a human cell

The spatial and structural arrangement of proteins determine virtually every process in human cells. We combined gentle subcellular fractionation by differential ultracentrifugation with cross-linking mass spectrometry to systematically map this cellular proteome architecture with residue-level evidence, identifying 164,146 residue-to-residue links in HEK293 cells. These links capture spatial protein arrangement at a resolution sufficient to pinpoint protein localizations at sub-organelle level, determine protein orientations within cellular membranes, and identify inter-organelle contact sites. The residue-level information provides evidence for 18,074 direct protein-protein interactions (PPIs), which we integrate into AlphaFold-based pipelines to nominate PPI-mediating short linear motifs and generate assembly models of large protein complexes. Guided by these spatial and structural readouts, we discover new PPIs within the endomembrane system that regulate the compartmental localization of trafficking machinery. Leveraging a network topology-driven strategy, we augment our HEK293 dataset with PPI data from different cell lines and methods, expanding the spatial and structural interactome of human cells.

systems biology↗

Sensory variation and behavioural degeneracy: a framework for interpreting heterogeneity in the gut-brain axis

Gut microbiome differences are frequently interpreted as reflecting underlying biological differences between individuals. When outcomes are mediated by behaviour, however, this mapping may be fundamentally non-unique. This limits causal inference in gut-brain research, where microbiome differences in autism and depression are routinely attributed to intrinsic neurobiology despite highly variable, overlapping findings. I built a minimal agent-based model grounded in the known sensory variation across the autism spectrum. Dietary behaviour emerges from latent sensory traits, including sensory drive, predictability preference, and context sensitivity, through reinforcement learning and environmental interaction. This behaviour shapes gut microbiome composition. Behavioural variation organizes endogenously into a continuum of specialist, opportunist, and explorer strategies that maps onto the autism sensory spectrum. The system is fundamentally degenerate. Similar microbiome states arise from distinct behavioural pathways. Similar dietary patterns emerge from divergent latent traits. This many-to-one mapping reflects the structural interaction of behaviour, learning, and environmental variability, not stochasticity alone. Microbiome similarity therefore does not uniquely identify underlying cause. As such, the model provides a theoretical framework for interpreting heterogeneity in gut microbiome research, particularly in autism, and generalizes to any condition where behaviour mediates between neural processes and ecological outcomes.

systems biology↗