Computational modeling of motile cilia generated cerebral flow dynamics in zebrafish embryo

Abstract

Background: Motile cilia are hair-like microscopic structures which move the fluids along the epithelial surfaces. Cilia cover a wide range of regions in the nervous system, such as the nasal cavity, spinal cord central canal, and brain ventricles. Motile cilia-driven cerebrospinal fluid (CSF) flow in the brain ventricles has an important role in the brain development. Embryos lacking motile cilia develop neurological defects due to altered CSF flow. Aim: To investigate the effect of motile-cilia motion on the altered CSF flow, and to understand the role of CSF flow in the brain development and physiology. Methods: The dynamics of motile-cilia driven flow is analyzed employing computational fluid dynamics (CFD) modeling. A 2D model is generated using the time-lapse microscopic movies showing movements of a fluorescently labeled motile-cilia in a zebrafish embryo (48-hour post-fertilization). The effects on the generated flow are elucidated by investigating the cilia beating angle, multiple cilia formations, and the phase difference between different ciliary beats. Results: Ciliary beating generated a directional flow in the form of a circulating vortex. The angle of ciliary beating significantly affected the flow velocity. As the angle between the wall and cilia decreases, the flow becomes more efficient by achieving higher velocities. Multiple cilia formations increased the flow velocity but the significance of multiple cilia is not as critical as the beating angle. Interestingly, phase difference between the multiple cilia beats increased the directional flow velocity. Conclusion: Motile-cilia generated flow dynamics are investigated, and it is concluded that out-of-phase multiple ciliary beating is the optimum form of beating in order to generate a directional flow