Title: Mechanical Instability Leading Epithelial Cell Delamination,
Abstract: We theoretically investigate the mechanical stability of three-dimensional
(3D) foam geometry in a cell sheet and apply its understandings to epithelial
integrity and cell delamination. Analytical calculations revealed that the
monolayer integrity of cell sheet is lost to delamination by a spontaneous
symmetry breaking, inherently depending on the 3D foam geometry of cells; i.e.,
the instability spontaneously appears when the cell density in the sheet plane
increases and/or when the number of neighboring cells decreases, as observed in
vivo. The instability is also facilitated by the delaminated cell-specific
force generation upon lateral surfaces, which are driven by cell-intrinsic
genetic programs during cell invasion and apoptosis in physiology. In
principle, this instability emerges from the force balance on the lateral
boundaries among cells. Additionally, taking into account the cell-intrinsic
force generation on apical and basal sides, which are also broadly observed in
morphogenesis, homeostasis, and carcinogenesis, we found apically/basally
directed cell delaminations and pseudostratified structures, which could
universally explain mechanical regulations of epithelial geometries in both
physiology and pathophysiology.