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Author response: A soft active matter models explains spiral epithelial cell migration on in-vivo corneas

Abstract

The mammalian cornea constantly regenerates its outer epithelial layer. Cells lost by abrasion are replaced by division of both corneal epithelial cells and stem cell populations around the corneal periphery, the limbus. Limbal-derived epithelial cells migrate into the cornea, maintaining equal rates of cell loss and replacement (the ‘XYZ hypothesis’). This process produces a striking stable spiral cell motion pattern across the corneal surface, with a central vortex. Here, we show that this spiral pattern can be explained by the interplay of limbus position, cell division, extrusion, and collective cell migration along the curved corneal surface. Using dissected LacZ mosaic murine corneas, we inferred the surface flow field by following stripe edges, revealing a tightening spiral. To explain these flow fields, we developed a cell-level in silico model treating corneal epithelial cells as soft, self-propelled particles with density-dependent proliferation and extrusion rates, and noisy alignment of migration direction. Even without global guidance cues, the model predicted stripes and spirals closely recapitulating experiment. A complementary continuum description generalised the XYZ hypothesis. Spiral formation was robust to curvature changes, but not topology, and sensitive to limbal stem cells and flocking alignment, showing how swarm physics on curved surfaces can explain tissue-scale biological processes.

Authors 4

  1. University of Aberdeen

    Affiliation as printed

    University of Aberdeen , School of Medicine , Medical Sciences and Nutrition •

  2. University of Dundee

    Affiliation as printed

    School of Life Sciences , University of Dundee , Dundee , DD1 5EH , United Kingdom •

    School of Science and Engineering , University of Dundee , Dundee , DD1 4HN , United Kingdom •

  3. University of Aberdeen

    Affiliation as printed

    University of Aberdeen , School of Medicine , Medical Sciences and Nutrition , Aberdeen AB25 2ZD , United Kingdom

    University of Aberdeen , School of Medicine , Medical Sciences and Nutrition •

  4. Leiden University · University of Dundee

    Affiliation as printed

    Lorentz Institute , LION , Leiden University , 2311 CA Leiden , Netherlands

    School of Science and Engineering , University of Dundee , Dundee , DD1 4HN , United Kingdom

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