Modeling tissue-scale ciliary transport and mixing in three-dimensional Newtonian flow

Mucociliary clearance is the primary defense mechanism in our respiratory system against aerosol pathogens and allergens. The rhythmic movement of cilia on airway-lining cells propels mucus flow, driving the movement of trapped particles. However, the impact of cilia density and distribution on mucociliary mixing and transport at the tissue scale remains poorly understood. In the present work, we present three-dimensional (3D) simulations of ciliary-driven mixing and transport of a Newtonian fluid as an approximation of mucus at the tissue scale. We investigate the influence of ciliary density, cilia cluster spacing, and metachrony on fluid mixing and transport. Our findings reveal that: (i) cilia clusters generate flow swirls whose size scales with ciliary density, (ii) a single cilia cluster generates horizontal and upward transport with horizontal mixing, (iii) optimal spacing between ciliary clusters enhances horizontal transport, and (iv) metachronic waves enhances mixing but reduces net transport. These findings provide useful insight into generic principles of cilia-driven transport in viscous fluids and may inform bio-inspired system design, while further work is needed to extend this work to physiologically realistic mucus transport.