Modeling the Impact of Cellular and Growth Factor Diffusivity on Lung Branching During Development
Abstract – Lung morphogenesis refers to the growth and development of the lung via a branching process that depends on bud formation and growth. Proper lung growth is attributed to Fibroblast Growth Factor 10 (FGF10) in the mesenchyme, which encourages cells in the epithelium to grow. Thus, a suitable diffusivity of the FGF10 and the cells is required for the best growth to sustain necessary gas exchange. Diseases like cystic fibrosis and idiopathic pulmonary disease can alter the production and viscosity of respiratory mucus, thus causing changes in diffusivity. This research seeks to mathematically simulate the proliferation of lung cells on a 1-dimensional axis with a reaction-diffusion model to understand the dynamics of cellular migration and growth in health and disease. The diffusivity of various parts of the simulation were varied to determine their impact on overall cellular proliferation. Epithelial diffusion was found to be the rate-limiting factor of lung formation and branching. These results suggest that disease states which limit cell migration can most adversely affect developmental pathways and also that therapeutic strategies that focus on improving cell migration might be the most impactful. Future directions include modeling in 2-dimensional and 3-dimensional space, the incorporation of other molecules that play a part in lung morphogenesis (such as Bone Marrow Protein and Sonic Hedgehog protein), and verification of these models with in vitro experiments and observations.
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