Effects of hydrostatic pressure on epithelial dome formation and stability

Abstract

Hydrostatic pressure in living organisms is crucial to the formation and stability of hollow structures in tissues and organs. However, the underlying mechanisms governing the collective cell responses to the pressure in these processes have not yet been fully understood. Here, we developed a hydrostatic pressure generator to produce various pressures of physiological magnitudes and explored their effects on dome structure formation on the epithelial monolayer. We found that the positive hydrostatic pressure promoted dome formation while the negative one suppressed it. The positive pressure induced cell autophagy and thus increased transepithelial electrical resistance, which elevated osmotic pressures inside the dome. In addition, the positive pressure induced reorganization of actin-cytoskeleton, which stabilized the cytoskeleton network and weakened cell-matrix adhesion. Interestingly, during dome expansion, the negative pressure promoted the expansion, which eventually led to the dome rupture; while the positive pressure suppressed the expansion and subsequent rupture. Our numerical simulations revealed that the negative pressure produced larger intercellular normal stress within the dome wall, making the dome more prone to rupture. These findings revealed the biophysical mechanisms by which hydrostatic pressure regulates dome formation and stability, and provided insights into the effect of external pressure on collective cell behaviors during tissue morphogenesis.