Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Kavli Institute for Systems, Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Trondheim, Norway; Department of Pharmaceutical Biosciences and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
Stephan Bialonski
Institute for Data-Driven Technologies, Aachen University of Applied Sciences, Jülich, Germany; Center for Advancing Electronics, Technical University Dresden, Dresden, Germany
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
Anton Solovev
Center for Advancing Electronics, Technical University Dresden, Dresden, Germany; Cluster of Excellence 'Physics of Life', Technical University Dresden, Dresden, Germany
Center for Advancing Electronics, Technical University Dresden, Dresden, Germany; Cluster of Excellence 'Physics of Life', Technical University Dresden, Dresden, Germany
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Kavli Institute for Systems, Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Trondheim, Norway
Motile cilia are hair-like cell extensions that beat periodically to generate fluid flow along various epithelial tissues within the body. In dense multiciliated carpets, cilia were shown to exhibit a remarkable coordination of their beat in the form of traveling metachronal waves, a phenomenon which supposedly enhances fluid transport. Yet, how cilia coordinate their regular beat in multiciliated epithelia to move fluids remains insufficiently understood, particularly due to lack of rigorous quantification. We combine experiments, novel analysis tools, and theory to address this knowledge gap. To investigate collective dynamics of cilia, we studied zebrafish multiciliated epithelia in the nose and the brain. We focused mainly on the zebrafish nose, due to its conserved properties with other ciliated tissues and its superior accessibility for non-invasive imaging. We revealed that cilia are synchronized only locally and that the size of local synchronization domains increases with the viscosity of the surrounding medium. Even though synchronization is local only, we observed global patterns of traveling metachronal waves across the zebrafish multiciliated epithelium. Intriguingly, these global wave direction patterns are conserved across individual fish, but different for left and right noses, unveiling a chiral asymmetry of metachronal coordination. To understand the implications of synchronization for fluid pumping, we used a computational model of a regular array of cilia. We found that local metachronal synchronization prevents steric collisions, i.e., cilia colliding with each other, and improves fluid pumping in dense cilia carpets, but hardly affects the direction of fluid flow. In conclusion, we show that local synchronization together with tissue-scale cilia alignment coincide and generate metachronal wave patterns in multiciliated epithelia, which enhance their physiological function of fluid pumping.
