Cellular and Tissue Level Modeling
CURRENT PROJECTS
MODELING THE IMPACT OF CHRONIC DISUSE ATROPHY ON MUSCLE REGENERATION AFTER INJURY
Disuse atrophy occurs after prolonged periods of mechanical unloading of skeletal muscle, leading to reductions in muscle mass and strength. Several clinical populations face disuse atrophy, like those on bed rest or in spaceflight. We know that several cell behaviors are impaired in unloaded environments, such as immune response and fibroblast adhesion, but it is unclear how these impairments collectively affect skeletal muscle regeneration. Using agent-based modeling, we hope to investigate how these altered cell behaviors in atrophied skeletal muscle influence regenerative capacity.
MODELING CELLULAR BEHAVIORS AND THE ROLE OF ESTROGEN SIGNALING DURING MUSCLE REGENERATION
Computational models are an ideal complement to experimental efforts for understanding complex phenomena such as muscle degeneration, regeneration, and remodeling, which emerge from the dynamic behaviors and interactions of individual, heterogeneous cells that are mediated by numerous biochemical signals. While our fundamental understanding of the individual cellular and subcellular behaviors of muscle cells has advanced, there remain no effective treatment methods to accelerate muscle regeneration and reduce fibrosis. In our lab, we use agent-based modeling to study the impact of cell behaviors, cytokine expression, and sex hormones on muscle regeneration. These models are used to test variations of growth factor levels to develop optimized treatments for muscle regeneration that account for variations in estrogen levels.
PREVIOUS PROJECTS
MODELING MUSCLE REGENERATION AND FIBER INTERACTIONS
Our agent-based models have captured dynamics of inflammation and regeneration following injuries of varying severity. These models incorporate macrophage, fibroblast, and SSC phenotypes along with cytokine diffusion, decay, and receptor-mediated interactions. These models were validated using in-vivo datasets to identify combinations of cytokines, such as HGF, VEGF-A, and TGF- β, that regulate injury-type specific recovery. In parallel, we have developed micromechanical models that quantify how stress and strain is transmitted through the muscle model. These models provide insight into how injury, injury site, architecture, and cell-mediated repair dictate functional outcomes.
FIBROSIS AND EXTRACELLULAR MATRIX MECHANICS
Fibrosis fundamentally alters muscle structure and function by remodeling the extracellular matrix (ECM), increasing stiffness, and limiting cellular movement. To quantify these changes, we integrate histology, scanning electron microscopy, and image-based finite-element modeling. In diseases, such as Duchenne Muscular Dystrophy, we have assessed collagen architecture and predicted behavior. These micro-scale models enable the framework to bridge cellular and fascicle level interactions with muscle material properties, providing insight into disease progression.