Integrative Models of Microorganism Motility

该项目涉及微生物的流体动力学和力产生机制，应用范围从真核鞭毛中的动力蛋白激活到致病螺旋体的运动。建立了将运动微生物的内部分子马达和弹性机制与粘性、不可压缩流体相耦合的计算模型。采用统一的计算方法来模拟纤毛和精子的内部轴丝机制、螺旋体内周质鞭毛的作用以及粘纤毛的相互作用。除了对单个生物体的动力学进行建模外，还可以研究生物体群体及其环境的集体水动力相互作用。即使假设生物体的波形是已知的，也很难分析柔性游动生物体所引起的移动边界问题。事实上，微生物的波形是由有机体的力产生机制、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涌现特性。研究人员开发了一个数学模型和一种数值方法来研究这个耦合的机械系统。计算流体力学中的现代方法被用来创造一个受控环境，在这个环境中可以对运动效应进行测量和可视化。微生物在流体中的运动在生理学中具有重要的基础作用。人类的生殖需要精子成功地通过男性和女性生殖道。致病螺旋体的强大移动能力使这些细菌能够有效地在粘性液体和粘膜表面移动。一个由数学家、计算科学家和实验生物学家组成的多学科研究小组协调他们的努力，研究许多系统中细胞运动的基本机制。这些系统包括纤毛和鞭毛、螺旋体(如那些莱姆病和梅毒的病原体)、细菌生物膜和呼吸道中的粘液-纤毛运输。更好地了解微生物的内部生物化学和生物物理机制是如何与它们活动的流体环境相耦合的，可以对细菌感染和不孕症治疗的药物设计产生影响。这个项目借鉴了许多学科的想法，如流体力学、科学计算、细胞生物学和数值分析。我们的多学科方法使我们在理解微生物运动方面取得了重大进展。此外，开发的算法和方法对研究其他生物流体动力学问题也很有用，并有助于高性能计算的专业知识。

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.