Migration and division in cell monolayers on substrates with topological defects

Collective movement and organization of cell monolayers are important for wound healing and tissue development. Recent experiments highlighted the importance of liquid crystal order within these layers, suggesting that +1 topological defects have a role in organizing tissue morphogenesis. We study fibroblast organization, motion and proliferation on a substrate with micron-sized ridges that induce +1 and −1 topological defects using simulation and experiment. We model cells as selfpropelled deformable ellipses that interact via a Gay-Berne potential. Unlike earlier work on other cell types, we see that density variation near defects is not explained by collective migration. We propose instead that fibroblasts have different division rates depending on their area and aspect ratio. This model captures key features of our previous experiments: the alignment quality worsens at high cell density and, at the center of the +1 defects, cells can adopt either highly anisotropic or primarily isotropic morphologies. Experiments performed with different ridge heights confirm a new prediction of this model: suppressing migration across ridges promotes higher cell density at the +1 defect. Our work enables new mechanisms for tissue patterning using topological defects.