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 self-propelled 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 prediction of this model: Suppressing migration across ridges promotes higher cell density at the +1 defect. Our work enables a mechanism for tissue patterning using topological defects without relying on cell migration.

Topological defects of integer charge in cell monolayers.

Many cell types spontaneously order like nematic liquid crystals, and, as such, they form topological defects, which influence the cell organization. While defects with topological charge ±1/2 are common in cell monolayers, defects with charge ±1, which are thought to be relevant in the formation of protrusions in living systems, are more elusive. We use topographical patterns to impose topological charge of ±1 in controlled locations in cell monolayers. We study two types of cells, 3T6 fibroblasts and EpH-4 epithelial cells, and we compare their behavior on such patterns, characterizing the degree of alignment, the cell density near the defects, and their behavior at the defect core. We observe density variation in the 3T6 monolayers near both types of defects over the same length-scale. By choosing appropriate geometrical parameters of our topographical features, we identify a new behavior of 3T6 cells near the defects with topological charge +1, leading to a change in the cells' preferred shape. Our strategy allows a fine control of cell alignment near defects as a platform to study liquid crystalline properties of cells.