3D shape of epithelial cells on curved substrates

Abstract

It is widely recognized that the shape of epithelial cells is determined by the tension generated by the actomyosin cortex and the adhesion of cells to the substrate and to each other. To account for these biological and structural contributions to cell shape, different physical models have been proposed. However, an experimental procedure that would allow a validation of a minimal physical model for the shape of epithelial cells in 3D has not yet been proposed. In this study, we cultured MDCK epithelial cells on substrates with a sinusoidal profile, allowing us to measure the shape of the cells on various positive and negative curvatures. We found that MDCK cells are thicker in the valleys than on the crests of sinusoidal substrates. The influence of curvature on the shape of epithelial cells could not be understood with a model using only differential apical, basal and lateral surface energies. However, the addition of an apical line tension was sufficient to quantitatively account for the experimental measurements. The model also accounts for the shape of MDCK cells that overexpress E-cadherin. On the other hand, when reducing myosin II activity with blebbistatin, we measured a saturation of the difference in cell thickness between valleys and crests, suggesting the need for a term limiting large cell deformations. Our results show that a minimal model that accounts for epithelial cell shape needs to include an apical line tension in addition to differential surface energies, highlighting the importance of structures that produce anisotropic tension in epithelial cells, such as the actin belt linking adherens junctions. In the future, our experimental procedure could be used to test a wider range of physical models for the shape of epithelia in curved environments, including, for example, continuous models.