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Migration and division in cell monolayers on substrates with topological defects

Kurmanbek Kaiyrbekov, Kirsten Endresen, Kyle T. Sullivan, Zhaofei Zheng, Yun Chen, Francesca Serra, Brian A. Camley

2023Proceedings of the National Academy of Sciences22 citationsDOIOpen Access PDF

Abstract

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.

Topics & Concepts

Topological defectTopology (electrical circuits)Cell divisionMorphogenesisRidgeMonolayerMaterials scienceCell migrationCellCell biologyBiophysicsNanotechnologyChemistryBiologyPhysicsCondensed matter physicsMathematicsGeneBiochemistryPaleontologyCombinatoricsCellular Mechanics and InteractionsMicro and Nano Robotics3D Printing in Biomedical Research
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