CAREER: Locomotion of Small Organisms in Complex Fluids

[0954084]理解动物的运动具有重要的实际意义和科学意义。尽管付出了很多努力，但关于流体流变学（如粘弹性）对小生物运动性的影响，许多问题仍未得到解答。这些问题的答案可能导致潜在的有用的应用跨越许多领域，如工程、机器人、物理和生物学。例如，对模式生物的运动调查可以为分析与肌肉萎缩症（MD）有关的新的和现有的突变提供有力的工具，这种疾病影响着全世界数百万人，但迄今为止尚无治愈方法。该项目旨在(1)提高我们对复杂介质（包括粘弹性流体）中控制线虫运动的力量的理解，以及(2)非侵入性地测量携带MD的健康和突变线虫的生物力学和材料特性。选择的生物体是线虫（线虫）隐杆线虫（C.） elegans。由于其体积小（L~ 1mm）和对各种流体环境的适应性，它是复杂流体中低雷诺数运动研究的有希望的候选者。秀丽隐杆线虫也是一种用于探索人类疾病的潜在原因和治疗方法的模式生物系统，因为它们的基因组已经完全测序。此外，秀丽隐杆线虫的运动是由95个肌肉细胞控制的，这些肌肉细胞在解剖结构和分子组成上都与脊椎动物的骨骼肌高度相似。这些肌肉细胞表达许多与人类肌肉营养不良相关的基因，如与肌营养不良蛋白和（Duchennes MD）和Dysferlin （Limb Girdle MD）同源的基因。这项研究有两个主要目的。第一部分致力于研究在低雷诺数条件下，表现出固体和类流体行为的流体（如粘弹性流体）对秀丽隐杆线虫运动的影响。许多相关的生物体在粘弹性流体中运动，如粘液、生物分子流体和悬浮液。然而，人们对弹性应力对生物体运动行为的影响知之甚少。重要的问题包括：(i)流体弹性应力如何影响低雷诺数下线虫的运动、运动学和游泳行为？（ii）在弹性应力和/或剪切速率依赖的黏度存在下，线虫游得更快还是更慢？（三）线虫是否通过改变游动的频率和幅度等步态来调整或适应流体环境？第二种方法是应用这些知识来估计游动线虫的生物力学和材料特性。通过估计这些特性，PI将能够对携带MD的野生型和突变型线虫进行表型分析，这最终将有助于开发定量、可靠的MD诊断工具。智力优势：该研究是基于PI之前在理解复杂流体流动现象方面的努力，并将做出新的有价值的基础和应用贡献。从基础的角度来看，PI将(1)使用高空间和时间分辨率的实验来表征复杂流体环境中的流动行为和线虫运动。这种定量的、基于工程的肌肉功能分析为肌肉生理学和其他疾病的研究提供了新的范式；(2)建立理论和数值模型来描述线虫的生物力学特征，以便无创地获得其材料特性的估计；(3)研究流体流变特性对线虫运动的影响。从应用的角度来看，PI将开发能够定量调查携带基因突变的线虫的诊断工具，包括与肌肉萎缩症相关的基因突变。由于秀丽隐杆线虫为定义环境应激信号的分子基础提供了许多优势，因此该研究项目将有助于更好地理解基于运动的疾病，如肌肉萎缩症。更广泛的影响：一个综合的研究和教育计划在于（流体）力学和生物学之间的丰富界面。它包括：(1)从没有工程研究生项目的传统黑人学院和大学招募本科生进行暑期研究实习。其中一个主要目标是增加历史上代表性不足的少数民族的参与，如非洲裔美国人、美洲原住民和西班牙裔美国人；(2)通过提供复杂流体和生物流体的新研究生课程以及研究机会来培养研究生；(3)让K-12教师参与研究和教育计划。最后，这项研究和教育计划的结果将被广泛传播，并将对社会产生潜在的重要利益。特别是，结果将增加对新的流体力学现象和某些类型的疾病的理解。

0954084ArratiaAn understanding of the locomotion of animals is of great practical and scientific importance. Despite much effort, many questions remain unanswered regarding the effects of fluid rheology (e.g. viscoelasticity) on the motility of small living organisms. Answers to these questions can lead to potentially useful applications spanning many fields such as engineering, robotics, physics, and biology. For example, motility investigations of model living organisms can provide a powerful tool for the analysis of new and existing mutations involved in Muscular Dystrophy (MD), a disease that affects millions of people worldwide but, to date, has no cure. This project aims to (1) advance our understanding of the forces governing nematode motility in complex media including viscoelastic fluids and to (2) measure non-invasively the biomechanical and material properties of healthy and mutant nematodes carrying MD. The organism of choice is the nematode (worm) Caenorhabditis (C.) elegans, which is a promising candidate for motility investigations at low Reynolds numbers in complex fluids due to their small size (L~ 1 mm) and adaptability to various fluidic environments. C. elegans is also a model biological system used to explore potential causes and treatments for human diseases because their genome has been completely sequenced. In addition, the motility of C. elegans is controlled by 95 muscle cells that are highly similar in both anatomy and molecular makeup to vertebrate skeletal muscle. These muscle cells express many genes associated with human muscular dystrophies, such as genes homologous to Dystrophin and (Duchennes MD) and Dysferlin (Limb Girdle MD). This research is motivated by two primary objectives. The first is devoted to the fundamental investigation of the effects of fluids that exhibit both solid and fluid-like behavior such as viscoelastic fluids on the motility of C. elegans in the low Reynolds numbers regime. Many relevant living organisms move in viscoelastic fluids such as mucus, and bio-molecular fluids, and suspensions. However, little is known about the effects of elastic stresses on the motility behavior of living organisms. Important questions include: (i) how do fluid elastic stresses affect the motility kinematic and swimming behavior of nematodes at low Reynolds numbers? (ii) Do nematodes swim faster or slower in the presence of elastic stresses and/or shear rate dependent viscosity? (iii) Do nematodes adjust or adapt to their fluidic environment by changing their swimming gaits such as frequency and amplitude? The second involves applying this knowledge to estimate the biomechanical and material properties of swimming nematodes. By estimating such properties, the PI will be able to phenotype wild-type and mutant nematodes carrying MD, which ultimately will contribute to developing quantitative, reliable diagnostic tools for MD. Intellectual Merit:The research is based on the PI's previous efforts in understanding complex fluid flow phenomena, and will make new valuable contributions that are both fundamental and applied. From a fundamental perspective, the PI will (1) use high spatial and temporal resolution experiments to characterize the flow behavior and nematode motion in complex fluidic environments. Such a quantitative, engineering based analysis of muscle function provides a new paradigm for the study of muscle physiology and other diseases; (2) develop theoretical and numerical models to characterize the biomechanics of nematodes in order to non invasively obtain estimates of their material properties; and (3) investigate the effects of fluid rheological properties on the motility of nematodes. From an applied perspective, the PI will develop diagnostic tools capable of quantitatively investigating nematodes carrying genetic mutations including those associated with Muscular Dystrophy. Since C. elegans offer many advantages for defining the molecular basis of environmental stress signaling, this research program will contribute to a better understanding of motility based diseases such as Muscular Dystrophy. Broader Impact:An integrated research and educational program lies at the rich interface between (fluid) mechanics and biology. It includes: (1) recruiting undergraduate students for summer research internships from Historically Black Colleges and Universities that do not possess an engineering graduate program. One of the main objectives is to increase the participation of historically under represented minorities such as African Americans, Native Americans, and Hispanics in research; (2) training graduate students by offering new graduate level courses in complex and bio-fluids as well as research opportunities; (3) involving K-12 teachers in the research and educational program. Finally, the results of this research and educational program will be broadly disseminated and will have potentially important benefits to society. In particular, the results will increase understanding of new fluid mechanics phenomena and certain types of diseases.