Effect of cyclic stretching on cell shape and division

In multicellular organisms, cell fate and tissue organization are greatly affected by the orientation of the cell division axis. Cell division is aligned perpendicular to the long axis of a cell - the so-called ‘Hertwig’s rule’. Because mechanical strains on cells cause arrangement of cytoskeleton molecules which determines cell shape, it is expected that mechanical strains also play an important role on the orientation of the cell division axis. In this study, we used a microfabricated cyclic stretching device to understand how mechanical strains affect the orientation of the cell division axis, which determines the spatial arrangement of daughter cells. When RPE-1 (retinal pigmented epithelial) cells were cyclically stretched during their prophase and prometa phase at various stretching magnitudes (5% and 10%) and frequencies (0.1-10 Hz), the cells’ aspect ratios were at their highest. Compared to unstretched cells with aspect ratios below 2.5, the stretched ones with aspect ratios higher than 4 better suited Hertwig’s rule by showing a good alignment of spindle angle to the perpendicular direction to the long axis of their cell bodies. These results suggest that mechanical strains play important roles in determining the cell division axis by affecting cell shape and orientation.