Fluctuation of cilia-generated flow on the surface of the tracheal lumen

Abstract

Although we inhale air that contains many harmful substances, including, for example, dust and viruses, these small particles are trapped on the surface of the tracheal lumen and transported towards the larynx by cilia-generated flow. The transport phenomena are affected not only by the time- and space-average flow field but also by the fluctuation of the flow. Because flow fluctuation has received little attention, we investigated it experimentally in mice. To understand the origin of flow fluctuation, we first measured the distribution of ciliated cells in the trachea and individual ciliary motions. We then measured the detailed flow field using a confocal micro-PTV system. Strong flow fluctuations were observed, caused by the unsteadiness of the ciliary beat and the spatial inhomogeneity of ciliated cells. The spreading of particles relative to the bulk motion became diffusive if the time scale was sufficiently larger than the beat period. Finally, we quantified the effects of flow fluctuation on bulk flow by evaluating the Peclet number of the system, which indicated that the directional transport was an order of magnitude larger than the isotropic diffusion. These results are important in understanding transport phenomena in the airways on a cellular scale.

Regional Differences in Mucociliary Clearance in the Upper and Lower Airways

“…In the mouse, the nasal epithelium (posterior nasopharynx) has about twice the density of ciliated cells (∼80% ciliation) as has the trachea (∼40% ciliation). There are numerous reports in the literature documenting that the murine trachea is very sparsely ciliated [30-37% (Pack et al, 1980;Klein et al, 2009;Kiyota et al, 2014)] and that ciliated cells in the trachea are found in scattered patches (Pack et al, 1980). In fact, Pack et al (1980) commented that in the murine trachea the ciliated cells "were so far apart that is difficult to envisage how such a mucous sheet would be propelled."…”

“…In the mouse, the nasal epithelium (posterior nasopharynx) has about twice the density of ciliated cells (∼80% ciliation) as has the trachea (∼40% ciliation). There are numerous reports in the literature documenting that the murine trachea is very sparsely ciliated [30–37% ( Pack et al, 1980 ; Klein et al, 2009 ; Kiyota et al, 2014 )] and that ciliated cells in the trachea are found in scattered patches ( Pack et al, 1980 ). In fact, Pack et al (1980) commented that in the murine trachea the ciliated cells “were so far apart that is difficult to envisage how such a mucous sheet would be propelled.” As it has been previously shown that there is a positive correlation between cilial density and the rate of MCC ( Smith et al, 2008 ; Xu and Jiang, 2015 ; Chatelin and Poncet, 2016 ; Leung et al, 2019 ), it is likely that the difference in the rate of MCC between the PNP and trachea is in large part a result of significantly more abundant ciliated cells in the PNP.…”

Elastohydrodynamic phase-lock in two rotating cilia

“…The sign of the phase difference is positive, suggesting that downstream cilium2 always takes the lead over upstream cilium1. This type of phase propagation (downstream to upstream) is similar to an antipletic metachronal wave, which is widely observed in nature (Kiyota et al, 2014;Sleigh, 1962).…”

Microscale imaging of cilia-driven fluid flow

“…PTV requires sufficiently high frame rates needed to accurately track particles. This speed limitation of scanning confocal may explain why although particle tracking velocimetry has been implemented in mucociliary flow imaging [167], the more common implementation of confocal fluorescence appears to be in static imaging of airway surface liquid structure [137]. …”

“…Because cilia themselves can be fluorescently labeled, using a rapid enough confocal microscope allows quantification of ciliary beat frequency by direct visualization of the cilia themselves [21,167,171]. Moreover, methods of measuring diffusivity such as fluorescent recovery after photobleaching (FRAP) and fluorescence correlation spectroscopy (FCS) require well-defined, reasonably Gaussian focal volumes to properly extract diffusion [65,172].…”