Mechanochemical dynamics of collective cells and hierarchical topological defects in multicellular lumens.

Collective cell dynamics is essential for tissue morphogenesis and various biological functions. However, it remains incompletely understood how mechanical forces and chemical signaling are integrated to direct collective cell behaviors underlying tissue morphogenesis. Here, we propose a three-dimensional (3D) mechanochemical theory accounting for biochemical reaction-diffusion and cellular mechanotransduction to investigate the dynamics of multicellular lumens. We show that the interplay between biochemical signaling and mechanics can trigger either pitchfork or Hopf bifurcation to induce diverse static mechanochemical patterns or generate oscillations with multiple modes both involving marked mechanical deformations in lumens. We uncover the crucial role of mechanochemical feedback in emerging morphodynamics and identify the evolution and morphogenetic functions of hierarchical topological defects including cell-level hexatic defects and tissue-level orientational defects. Our theory captures the common mechanochemical traits of collective dynamics observed in experiments and could provide a mechanistic context for understanding morphological symmetry breaking in 3D lumen-like tissues.