Mechanisms of Monolayer Migration

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DESCRIPTION (provided by applicant): This small project will complete testing and development of an agent-based computational model of multi-cell migration in the classic scratch wound assay. The model attempts to mimic experiments on a simple immortal cell type (3T3-L1 fibroblasts) without free parameters. L1 cells are used because these cells exhibit stable growth and migration characteristics upon repeated passages, and reproducibly heal wounds in a steady, collective fashion despite their lack of specialized adhesive junctions. Collective migration occurs in a variety of medically important circumstances including wound healing, angiogenesis, and metastasis by some cancers. Thus the development of a quantitative understanding of the mechanisms of collective migration in the L1 system should provide a baseline for interpreting and/or modulating the behavior of more complex cell types. To achieve a predictive model the project will proceed successively through two aims. Early efforts will focus on the construction of a specialized multiphase interference microscope for the real-time measurement of cell height during wound healing experiments. Cell height measurements are needed because the existing model predicts that the breakdown of collective migration into cell scatter occurs once cells become fully spread on the substrate. The remaining efforts will test this and other predictions of the current computational model, measure missing parameters, and refine the model to arrive at a demonstrably predictive model of monolayer migration for a basic cell type. PUBLIC HEALTH RELEVANCE: This project will develop a predictive computational model of collective cell migration. Because collective cell migration is fundamental in tissue repair and development, the model can serve as a platform for rationale design of regenerative and anti-tumor therapies and tissue-engineered surfaces.