Riding the cell jamming boundary: Geometry, topology, and phase of human corneal endothelium.

It is important to assess the viability of eye-banked corneas prior to transplantation due to inherent senescence and known loss of endothelial cells during surgical manipulation. Corneal endothelial cells have a complex basal and paracellular shape making them challenging to accurately measure, particularly in oedematous ex vivo tissue. This study used calibrated centroidal Voronoi Diagrams to segment cells in images of these human corneas, in order to characterize endothelial geometry, topology, and phase. Hexagonal cells dominated the endothelia, with most comprised of five different pleomorphs exhibiting self-similar topological coarsening through most of the endothelial cell density range. There was a linear relationship between cell size and shape, though cells with greater than six sides were present in larger proportions than cells with less. Hexagonal cell regularity was stable and largely independent of density. Cell and tissue phase was also examined, using the cell shape index relative to the recently discovered 'cell jamming' phase transition boundary. Images showed fluid endothelia with a range of shape indices spanning the boundary, independent of density but dependent on hexagonal regularity. The cells showed a bimodal distribution centred at the boundary, with the largest proportion of cells on the fluid side. A shoulder at the boundary suggested phase switching via shape transformation across the energy barrier, with cells either side having distinctly different size and shape characteristics. Regular hexagonal cells were closest to the boundary. This study showed the corneal endothelium acts as a glassy viscous foam characterized by well-established physical laws. Endothelial cell death transiently and locally increases cell fluidity, which is subsequently arrested by jamming of the pleomorphically diverse cell collective, via rearrangement and shape change of a small proportion of cells, which become locked in place by their neighbours thereby maintaining structural equilibrium with little energy expenditure.