Motile cilia and flagella are dynamic, elastic, biological structures that exhibit rhythmic motion. Through coordinated beating, cilia in the lung and respiratory tract help to clear the airway of potentially harmful particles and mucus. Impaired cilia motion can result in serious respiratory infection. This impairment can be caused by an altered fluid environment, a characteristic of cystic fibrosis, by defects in the cilia themselves as with primary ciliary dyskinesia, or by other respiratory diseases. Similarly, a sperm is only able to reach and fertilize an egg if its flagellum can propel it forward; impaired motility results in infertility. Cilia and sperm beating is highly dependent on the fluid environment, which contains fibrous, protein networks as well as chemical signals. Understanding this relationship between elastic structure and heterogeneous fluid is vital for development of delivery strategies for inhaled drugs and medicines, new contraceptives, and aiding in infertility due to reduced sperm motility. This project will focus on the development of new computational models and numerical methods that account for these fibrous, protein networks within the fluid to infer in vivo behavior of cilia and sperm.

Recent experiments have shown that i) sperm-flagella waveforms are altered when immersed in fluids containing networks of large proteins and also with flagellar calcium concentration, ii) the previously-considered `watery' fluid surrounding airway cilia actually contains a network of large proteins, or, 'brush'. This project will focus on identifying emergent waveforms of sperm flagella and airway cilia when nonplanar bending and internal flagellar biochemistry are taken into account. Cilia and flagella will be modeled as slender, elastic, structures immersed in a fluid governed by the Brinkman equation. A regularized framework and fundamental solutions will be used to derive new numerical methods for various confined geometries. The new numerical methods will be computationally-efficient and developed for use on high-performance computing systems. This research will identify factors that modulate sperm progression towards the egg, explore various waveforms of cilia and sperm, and investigate how a 'brush' in the fluid surrounding cilia might affect transport of particles within that fluid.

Agency
National Science Foundation (NSF)
Institute
Division of Mathematical Sciences (DMS)
Type
Standard Grant (Standard)
Application #
1413110
Program Officer
Junping Wang
Project Start
Project End
Budget Start
2014-08-15
Budget End
2017-07-31
Support Year
Fiscal Year
2014
Total Cost
$150,000
Indirect Cost
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