Synchronization of mammalian motile cilia in the brain with hydrodynamic forces

Motile cilia are widespread across the animal and plant kingdoms, displaying complex collective dynamics central to their physiology. Their coordination mechanism is not generally understood, with pre-vious work mainly focusing on algae and protists. We study here the synchronization of cilia beat in multiciliated cells from brain ven-tricles. The response to controlled oscillatory external flows shows that strong flows at a similar frequency to the actively beating cilia can entrain cilia oscillations. We find that the hydrodynamic forces required for this entrainment strongly depend on the number of cilia per cell. Cells with few cilia (up to five) can be entrained at flows comparable to the cilia-driven flows reported in vivo. Simulations of a minimal model of cilia interacting hydrodynamically show the same trends observed in cilia. Our results suggest that hydrody-namic forces between cilia are sufficient to be the mechanism behind the synchronization of mammalian brain cilia dynamics.\n\nSignificance StatementIt is shown experimentally, and also reproducing key qualitative results in a minimal mechanistic model simulated numerically, that in the motile cilia of the brain hydrodynamic forces of the magnitude that cilia themselves can generate are sufficient to establish the coordination of dynamics which is so crucial phys-iologically. This is the first experiment of its kind on multicilated cells, the key result is the unexpected importance of cilia num-ber per cell, with cells with fewer cilia much more susceptible to external flows. This finding changes the way in which we think about the question of collective cilia beating - it is not correct to simply examine isolated cilia and draw conclusions about the behaviour of cilia assemblies in multiciliated cells.