Nuclear Packing Sets Fluidity Along the Epithelial to Mesenchymal Spectrum

Abstract

Investigations of jamming in cancer have produced numerous phase diagrams intending to map fluidity across the epithelial-to-mesenchymal transition (EMT). Here, we use coalescence of homotypic and heterotypic multicellular spheroids to examine and carefully probe these phase spaces. Small changes in cellular EMT status result in full traversal of the solid-to-fluid continuum. We propose that stiff nuclei impede cell motion and spheroid coalescence and find that by softening nuclei, fluidization of an otherwise solid-like system occurs. Changes in fluidity during coalescence is fully captured by static cellular properties, such as internuclear spacing and nuclear shape, that can be assessed in individual non-interacting spheroids. We combine these quantities into an effective nuclear packing metric that depends on nuclear occupancy and nuclear elongation. Together, these findings reveal that nuclear morphology and packing act as important indicators and determinants of fluidity.