Integrative Models of Microorganism Motility

微生物运动的综合模型

• 批准号: 0201063
• 负责人: Lisa Fauci
• 金额: $ 145万
• 依托单位: Tulane University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0201063&HistoricalAwards=false
• 关键词: Integrative; Models; Microorganism; Motility

This project concerns the fluid dynamics and force-generating mechanisms of microorganisms, with applications ranging from dynein activation in a eucaryotic flagellum to the motility of pathogenic spirochetes. Computational models are developed that couple the internal molecular motors and elastic mechanisms of motile microorganisms with a viscous, incompressible fluid. A unified computational approach is adopted to model the internal axoneme mechanics of cilia and spermatozoa, the action of the internal periplasmic flagella of spirochetes, as well as mucociliary interactions. In addition to modeling the dynamics of a single organism, the collective hydrodynamic interactions of groups of organisms and their environment can be examined. The moving boundary problem posed by a flexible, swimming organism is very difficult to analyze, even when an organism's waveform is assumed to be known. In fact, the waveform of a microorganism is an emergent property of the coupled nonlinear system consisting of the organism's force-generating mechanisms, its passive elastic structure, and the external fluid dynamics. The investigators develop a mathematical model and a numerical method designed to study this coupled mechanical system. Modern methods in computational fluid dynamics are used to create a controlled environment where the measurement and visualization of locomotive effects can be made.The motion of microorganisms in fluid is of fundamental importance in physiology. Human reproduction requires the successful journey of spermatozoa through both the male and female reproductive tracts. The robust locomotory ability of pathogenic spirochetes enable these bacteria to efficiently move through viscous fluids and mucosal surfaces. A multidisciplinary research team of mathematicians, computational scientists and experimental biologists coordinates their efforts to investigate the fundamental mechanics of cell motility in a number of systems. These systems include cilia and flagella, spirochetes (such as those that are the causative agents of Lyme disease and syphilis), bacterial biofilms and mucus-ciliary transport in the respiratory tract. A greater understanding of how the internal biochemistry and biophysical mechanisms of microorganisms are coupled to the fluid environment in which they move can have an impact on drug design for bacterial infection as well as infertility treatment. This project draws ideas from many disciplines such as fluid mechanics, scientific computing, cell biology, and numerical analysis. Our multidisciplinary approach enables significant progress in the understanding of microorganism motility. Furthermore, the algorithms and methods developed are useful in studying other biofluiddynamic problems and contribute to expertise in high performance computing.

该项目涉及微生物的流体动力学和力生成机制，其应用从桉树鞭毛中的动力蛋白激活到致病性螺旋体的运动性。开发了计算模型，将动向微生物的内部分子电动机和弹性机制与粘性，不可压缩的流体融为一体。采用了一种统一的计算方法来对纤毛和精子的内部轴突力学进行建模，即螺旋体内部周质鞭毛的作用以及粘膜纤毛相互作用。除了模拟单个生物体的动力学外，还可以研究生物体及其环境的集体流体动力相互作用。即使假定有机体的波形已知，也很难分析由灵活的游泳生物带来的移动边界问题。实际上，微生物的波形是由生物体生成机制，其被动弹性结构和外部流体动力学组成的耦合非线性系统的新兴特性。研究人员开发了一种数学模型和一种用于研究这种耦合机械系统的数值方法。计算流体动力学中的现代方法用于创建一个受控的环境，可以在其中进行测量和可视化机车效应。在生理学中，微生物在流体中的运动至关重要。人类的繁殖需要精子通过男性和女性生殖道的成功旅程。病原螺旋体的强大运动能力使这些细菌能够有效地穿过粘性液体和粘膜表面。数学家，计算科学家和实验生物学家的多学科研究团队协调了他们在许多系统中调查细胞运动基本机制的努力。这些系统包括纤毛和鞭毛，螺旋体（例如那些是莱姆病和梅毒的致病药物），呼吸道中的细菌生物膜和粘液 - 丝状运输。更了解微生物的内部生物化学和生物物理机制如何与它们移动的流体环境结合在一起，可能会影响细菌感染以及不育治疗的药物设计。该项目从许多学科中汲取了想法，例如流体力学，科学计算，细胞生物学和数值分析。我们的多学科方法在理解微生物运动能力方面可以取得重大进展。此外，开发的算法和方法可用于研究其他生物荧光问题，并有助于高性能计算方面的专业知识。