Physics of Motility of Bacteria Living in Mucus Gels

建议的研究重点是了解细菌在非牛顿粘弹性凝胶中运动的基本物理，并将运动与介质的粘弹性属性相关联。使用引起溃疡的幽门螺杆菌在粘蛋白凝胶中，我们将探索两种运动模式：在中性pH下的溶液中的翻译运动，和在低pH下的凝胶中的纯旋转而不平移。我们将应用最先进的成像技术，如双光子显微镜和单颗粒和多颗粒跟踪，定量测量细菌运动的动力学及其对环境局部微流变学的影响。受细菌感染的凝胶的机械和流变性的整体或整体变化将由振荡剪切流变学确定。对野生型幽门螺杆菌与缺乏特定受体或鞭毛的突变体以及不同体型的比较研究，将使我们能够评估在这个复杂的生命系统中起作用的许多变量的影响。实验研究将得到对细菌运动和凝胶中鞭毛动力学的计算分析和理论建模的补充，以提供对运动中所涉及的速度、力和扭矩的定量估计，并了解运动如何与粘弹性相关的基本物理学。这些结果对凝胶中的运动性起关键作用的许多生物医学应用具有潜在的相关性，例如在幽门螺杆菌感染胃粘液导致溃疡和癌症的过程中，在三维凝胶基质中培养细菌和细胞，在人工组织的抗菌水凝胶的设计中，以及在纳米和微型游泳者和旋转体的开发中。该研究项目涉及具有理论物理、生物医学成像、微生物学和胃肠病学专业知识的合作者，将为在生物物理、流体动力学和微生物学、生物化学和分子生物学领域的研究生和本科生提供一个独特的多学科培训机会。将开发关于细菌运动的视频和简单的分析工具，用于本科课程和演示目的。我们将利用我们团队的多样性和研究主题的广泛吸引力，开展外联活动，向包括当地高中和少数族裔和其他社区团体在内的更广泛的受众介绍情况，并招募妇女和少数族裔本科生和高中生参与研究。

The focus of the proposed research is to understand the fundamental physics of bacterial motility in a non-Newtonian, viscoelastic gel and to correlate the motility with the viscoelastic properties of the medium. Using the ulcer causing bacterium H. pylori in mucin gels we will explore two regimes of motion: translational motion in solutions at neutral pH, and pure rotation without translation in gels at low pH. We will apply state-of-the-art imaging techniques such as two-photon microscopy and single and multi-particle tracking for quantitative measurements of the dynamics of the motion of the bacterium and its impact on the local micro-rheology of its environment. Global or bulk changes in the mechanical and rheological properties of the bacteria infected gel will be determined by oscillatory shear rheology. Comparative studies of the wild-type H. pylori bacteria with mutants deficient in specific receptors or flagella, as well as with different body shapes, will enable us to assess the effect of the many variables at play in this complex living system. The experimental studies will be complemented by computational analysis and theoretical modeling of bacterial motility and flagella dynamics in gels to provide quantitative estimates of the velocity, forces, and torques involved in the motion and understand the underlying physics of how the motion correlates with the viscoelasticity. The results have potential relevance to many biomedical applications where motility in a gel plays a key role, such as in the infection of stomach mucus by H. pylori which leads to ulcers and cancer, to culturing of bacteria and cells in 3-dimensional gel matrices, in the design of bacterial resistant hydrogels for artificial tissues, and in the development of nano- and microscale swimmers and rotators. The research project, involving collaborators with expertise in theoretical physics, biomedical imaging, microbiology, and gastroenterology, will provide a unique opportunity for multidisciplinary training of graduate and undergraduate students in the areas of biophysics, fluid dynamics and microbiology, biochemistry and molecular biology. Videos on bacterial motility and simple analysis tools will be developed for use in undergraduate courses and for demonstration purposes. We will take advantage of the diversity of our team, and the broad appeal of the research topic, to do outreach activities involving presentations to a broader audience, including local high schools, and minority and other community groups and to recruit women and minority undergraduate and high school students to participate in the research.