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Abstract

Cell migration plays an important role in the development and maintenance of multicellular organisms. Factors that induce cell migration and mechanisms controlling their expression are important for determining the mechanisms of factor-induced cell migration. Despite progress in the study of factor-induced cytotaxis, including chemotaxis and haptotaxis, precise control of the direction of cell migration over a wide area has not yet been achieved. Success in this area would update the cell migration assays, superior cell separation technologies, and artificial organs with high biocompatibility. The present study therefore sought to control the direction of cell migration over a wide area by adjusting the three-dimensional shape of the cell scaffold. The direction of cell migration was influenced by the shape of the cell scaffold, thereby optimizing cell adhesion and protrusion. Anisotropic arrangement of these three-dimensional shapes into a periodic structure induced unidirectional cell migration. Three factors were required for unidirectional cell migration: 1) the sizes of the anisotropic periodic structures had to be equal to or lower than the size of the spreading cells, 2) cell migration was restricted to a runway approximately the width of the cell, and 3) cells had to be prone to extension of long protrusions in one direction. Because the first two factors had been identified previously in studies of cell migration in one direction using two-dimensional shaped patterns, these three factors are likely important for the mechanism by which cell scaffold shapes regulate cell migration.