Structural characterization and statistical-mechanical model of epidermal patterns

Abstract

In proliferating epithelia of mammalian skin, cells of irregular polygonal-like shapes pack into complex nearly flat two-dimensional structures that are pliable to deformations. In this work, we employ various sensitive correlation functions to quantitatively characterize structural features of evolving packings of epithelial cells across length scales in mouse skin. We find that the pair statistics in direct and Fourier spaces of the cell centroids in the early stages of embryonic development show structural directional dependence, while in the late stages the patterns tend towards statistically isotropic states. We construct a minimalist four-component statistical-mechanical model involving effective isotropic pair interactions consisting of hard-core repulsion and extra short-ranged soft-core repulsion beyond the hard core, whose length scale is roughly the same as the hard core. The model parameters are optimized to match the sample pair statistics in both direct and Fourier spaces. By doing this, the parameters are biologically constrained. Our model predicts essentially the same polygonal shape distribution and size disparity of cells found in experiments as measured by Voronoi statistics. Moreover, our simulated equilibrium liquid-like configurations are able to match other nontrivial unconstrained statistics, which is a testament to the power and novelty of the model. We discuss ways in which our model might be extended so as to better understand morphogenesis (in particular the emergence of planar cell polarity), wound-healing, and disease progression processes in skin, and how it could be applied to the design of synthetic tissues.