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Avelino Da Costa1 2 Ramesh Subbiah3 4 Kwideok Park3 4 In-Suk Choi1 2

1, Korea Institute of Science and Technology, Seoul, , Korea (the Republic of)
2, KIST School, Korea University of Science and Technology, Seoul, , Korea (the Republic of)
3, Korea University of Science and Technology, Seoul, , Korea (the Republic of)
4, Korea Institute of Science and Technology, Seoul, , Korea (the Republic of)

Micro-environment of natural tissue presents the arrangement of cells including cell-matrix adhesion, migration and proliferation in three dimensional (3D) circumstances. Biological signals will be transmitted between cells to rebuild the damaged spot when the tissue is injured. The phenomenon behind this rebuilding process is still unknown and more studies need to be done in order to deeply elucidate cellular behaviors in natural tissue environment. In this study, we demonstrate the novel migration patterns of fibroblasts on curved edge, sharp edge and complex structure with confined geometry of 3D microgaps. Fibroblasts establish formation of stacking-up and bridge respectively on curved edge and sharp edge microgaps. Furthermore, fibroblast formed middle bridge and simultaneous stacking-up-bridge formation on complex structures. This dynamic behavior of the cells is due to cell proliferation, collective cell migration, cell-cell adherens junctions, extension of filopodia and contractility of myosin II. We suggest that these findings could guide us in understanding the mechanisms of guiding migration patterns and behaviors of cells on 3D substrates with different geometries. We hope the implications of our study can be applied for building effective biological scaffolds such as wound healing and tissue regeneration.

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