Integer topological defect annihilations drive polar ordering of epithelial monolayers

The ability of epithelial monolayers to self-organize into a dynamic polarized state is essential for tissue regeneration, development, and tumor progression. However, the mechanisms governing long-range polar ordering in biological tissues remain unclear. Here we investigate the self-organizing behavior of quiescent epithelial monolayers that transit from a disordered, static state to a dynamic state with long-range polar order upon growth factor exposure. We demonstrate that the heightened self-propelled activity of monolayer cells leads to formation of ±1 topological defect pairs that subsequently undergo sequential annihilation, ultimately driving the spread of long-range polar order throughout the system. A computational model, which treats the monolayer as an active elastic solid, accurately replicates this behavior, and weakening of cell-to-cell interactions impedes defect annihilation and polar ordering. Furthermore, we have identified a set of fundamental rules that describe how topological defects can function as local organizers to spread order through the system. Lastly, we show that transient proliferation and re-annihilation of defect pairs facilitate a 180 degrees reorientation of the collective cell flow. Our study reveals a crucial role of topological defects in generating collective motion with long-range order, and provides insights into the underlying principles of active matter physics in biological systems.