Aerospace and Mechanical Engineering, University of Southern California, Los Angeles, CA 90089.
Department of Mathematics, University of Michigan, Ann Arbor, MI 48109.
Proc Natl Acad Sci U S A. 2022 Nov 8;119(45):e2214413119. doi: 10.1073/pnas.2214413119. Epub 2022 Nov 2.
Ciliated tissues, such as in the mammalian lungs, brains, and reproductive tracts, are specialized to pump fluid. They generate flows by the collective activity of hundreds of thousands of individual cilia that beat in a striking metachronal wave pattern. Despite progress in analyzing cilia coordination, a general theory that links coordination and fluid pumping in the limit of large arrays of cilia remains lacking. Here, we conduct in silico experiments with thousands of hydrodynamically interacting cilia, and we develop a continuum theory in the limit of infinitely many independently beating cilia by combining tools from active matter and classical Stokes flow. We find, in both simulations and theory, that isotropic and synchronized ciliary states are unstable. Traveling waves emerge regardless of initial conditions, but the characteristics of the wave and net flows depend on cilia and tissue properties. That is, metachronal phase coordination is a stable global attractor in large ciliary carpets, even under finite perturbations to cilia and tissue properties. These results support the notion that functional specificity of ciliated tissues is interlaced with the tissue architecture and cilia beat kinematics and open up the prospect of establishing structure to function maps from cilium-level beat to tissue-level coordination and fluid pumping.
纤毛组织,如哺乳动物的肺部、大脑和生殖器官,具有专门的泵送液体的功能。它们通过成千上万根纤毛的集体活动产生流动,这些纤毛以惊人的同步波状模式进行拍打。尽管在分析纤毛协调方面取得了进展,但在大量纤毛的极限情况下,将协调与泵送液体联系起来的一般理论仍然缺乏。在这里,我们通过结合活性物质和经典 Stokes 流的工具,对数千个具有水力相互作用的纤毛进行了计算机模拟实验,并在无穷多独立拍打纤毛的极限情况下发展了连续体理论。我们发现,无论是在模拟还是在理论中,各向同性和同步的纤毛状态都是不稳定的。无论初始条件如何,都会出现行波,但波和净流动的特征取决于纤毛和组织的特性。也就是说,即使对纤毛和组织特性进行有限的扰动,同步相位协调在大纤毛地毯中仍然是一个稳定的全局吸引子。这些结果支持了这样一种观点,即纤毛组织的功能特异性与组织架构和纤毛拍打运动学交织在一起,并为从纤毛级拍打到组织级协调和泵送液体的结构到功能图谱的建立开辟了前景。