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Description
Collective cell migration is vital for tissue growth and maintenance in processes such as morphogenesis and wound healing, as well as other mechanisms in the body such as cancer metastasis. Migration as a collective occurs when sheets, streams, or clusters of cells are led through the extracellular matrix (ECM) by “leader” cells, and use intercellular communication, such as mechanotransduction and chemotactic signaling. Certain ECM properties that have been shown to play a significant role in cell migration include fiber stiffness, fiber density, fiber alignment, fiber diameter, ECM topology, bond density, and chemical signaling. While experimental results have provided insight on which ECM properties affect migration, the mechanics of collective cell migration in 3D are still not well understood. Currently, various models are being explored in order to better understand migration in its fuller scope. In our model, we chose to stochastically and temporarily generate ECM fibers as guides for movement, and pass intercellular forces through neighboring cells in contact. We chose parameters that have been proven to be experimentally significant, such as fiber density, fiber alignment, and adhesive force strength. Cluster parameters tested were cluster size and leader scenarios, with the simulations running until cluster dissociation. The aim of this research was to simulate clusters of cells migrating long-term in 3D with both cell-cell and cell-matrix interactions. We found that cluster mean-square-displacement (MSD), cluster speed, cluster lifetime, and cluster persistence length vary as the ECM conditions are modulated, reinforcing the idea that not only is single cell migration affected by ECM conditions, but that collective cell migration is as well. In addition, changes in cluster conditions were found to affect cluster migration. We believe our physics-based computational model further develops the concepts of cell migration, and with it we were able to determine which simulated scenarios could significantly affect migration in experimental research.
