Collaborative Research: Computational Models of Cilia and Flagella in a Brinkman Fluid

合作研究：Brinkman 流体中纤毛和鞭毛的计算模型

• 批准号: 1413078
• 负责人: Karin Leiderman
• 金额: $ 14.98万
• 依托单位: University of California - Merced
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2017-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1413078&HistoricalAwards=false
• 关键词: Collaborative; Research; Computational; Models; Cilia

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.

纤毛和鞭毛是动态的，弹性的生物结构，表现出节奏运动。通过协调的跳动，苏里亚在肺中和呼吸道有助于清除潜在有害颗粒和粘液的气道。纤毛运动受损会导致严重的呼吸道感染。这种障碍可能是由于纤维化环境的改变，囊性纤维化的特征，纤毛本身的缺陷，就像原发性睫状运动障碍或其他呼吸道疾病一样。同样，如果精子能够将其鞭毛推动，只能将其伸入并施肥。运动受损会导致不孕症。纤毛和精子跳动高度取决于含有纤维的蛋白质网络以及化学信号的流体环境。了解弹性结构与异构液之间的这种关系对于开发吸入药物和药物的输送策略，新的避孕药具以及由于精子运动降低而有助于不育。 该项目将着重于开发新的计算模型和数值方法，这些方法解释了这些纤维状的蛋白质网络，以推断纤毛和精子的体内行为。进行的实验表明，i）精子 - 弗拉格葡萄鼠波形在含有大型蛋白质的流体以及以前的弗拉格尔钙化网络中，以前的cally cally cally cally cally cally'in II）在含水中变化。气道纤毛实际上包含大型蛋​​白质网络，或“刷子”。当考虑到非平面弯曲和内部鞭毛生物化学时，该项目将着重于确定精子鞭毛和气道纤毛的新兴波形。纤毛和鞭毛将建模为细长，弹性，结构，沉浸在由边缘方程控制的流体中。正则化框架和基本解决方案将用于为各种限制几何形状提供新的数值方法。新的数值方法将具有计算效率，并开发用于高性能计算系统。这项研究将确定调节精子向鸡蛋进展的因素，探索纤毛和精子的各种波形，并研究纤毛周围流体中的“刷子”如何影响该液体中颗粒的运输。