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.
Elife. 2023 Jan 26;12:e77701. doi: 10.7554/eLife.77701.
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.
纤毛是一种毛发状的细胞延伸物，周期性地摆动以在体内各种上皮组织中产生液流。在密集的多纤毛地毯中，纤毛表现出它们的拍打协调，形成行波蠕动，这一现象据称增强了流体的输送。然而，多纤毛上皮中纤毛如何协调它们的规则拍打以移动流体仍然理解不足，特别是由于缺乏严格的量化。我们结合实验、新的分析工具和理论来解决这一知识差距。为了研究纤毛的集体动力学，我们研究了斑马鱼鼻和脑的多纤毛上皮。我们主要关注斑马鱼的鼻子，因为它与其他纤毛组织具有保守的特性，并且可以更方便地进行非侵入性成像。我们揭示了纤毛仅在局部同步，并且局部同步域的大小随着周围介质的粘度增加而增加。尽管同步仅在局部发生，但我们观察到行波蠕动在整个斑马鱼多纤毛上皮中的全局模式。有趣的是，这些全局波方向模式在个体鱼之间是保守的，但左右鼻子不同，揭示了行波协调的手性不对称性。为了理解同步对泵送流体的影响，我们使用了一个规则纤毛阵列的计算模型。我们发现局部行波同步可防止立体碰撞，即纤毛之间的碰撞，并在密集的纤毛地毯中改善了流体泵送，但几乎不影响流体流动的方向。总之，我们表明局部同步与组织尺度的纤毛排列一起产生多纤毛上皮中的行波蠕动模式，这增强了它们的流体泵送生理功能。
