Collaborative Research: Controlled Investigation of Micro- and Nanoscale Contact Interactions Between Microbes and Biomaterials Using Artificial Bacteria

在正常的生物过程和疾病中，移动的细菌和细胞通过非常密集的长分子环境进行运输。例如，精子在繁殖过程中穿过粘液，鼻子、肺或肠道的细菌在感染过程中穿透粘液，土壤和海洋细菌通过长链分子的细菌垫进行迁移。粘液分子和身体其他分子的长度通常与微生物的长度相同。这意味着微生物和分子之间的个体和不可预测的相互作用改变了微生物的运动方式。实验证据表明，微生物通过这些材料的运输可能主要是与单个分子的直接接触相互作用。接触相互作用难以测量，其对运动的影响也难以量化。这项研究的总体目标是量化直接接触相互作用对细菌推进的影响。这项研究将使用新型人工细菌、“微型机器人”和人造粘液来发现哪种接触相互作用主导了运输。这些数据将提高我们理解、甚至控制微生物在现实环境中的运动和传播的能力。调查人员将与当地K-12学生一起开展一个名为“像微生物一样移动”的推广项目。外展的目标是激发学生对细菌流动性的新理解，并鼓励他们在以后的教育中走上科学或技术（STEM）的道路。了解微生物运输的纳米力学也将提高我们控制疾病和了解正常细菌行为的能力。与游泳微生物的微观结构相互作用主要是通过流体动力学和力学模型来研究的。对于静电力、范德华引力和生物化学键介导的接触相互作用的作用，还没有深入的研究。这项研究将通过结合新的微型机器人人工细菌系统和一种新型半合成粘液来促进对细菌运输的理解，从而实现良好的控制和表征实验。人工模型允许控制密度、刚度、表面电荷、表面化学和微力学特性，以阐明流体动力学、近距离和纳米级接触相互作用对微生物通过生物介质运输的相对重要性。数值模拟将用于将相互作用整合到运输的定量模型中。最后，将观察到天然细菌在定义良好的生物材料中移动，并将其行为与人工系统中观察到的行为相关联，以确定哪些接触相互作用对生物学相关场景最重要，测试接触相互作用主导生物体微观结构对细菌游泳影响的假设。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Moving bacteria and cells transport themselves though very dense environments of long molecules during normal biological processes and disease. Examples are sperm that travel through mucus in reproduction, bacteria of the nose, lung or gut penetrating mucus during infection, and soil and oceanic bacteria migrating through a bacterial mat of long-chain molecules. The molecules of mucus and other molecules of the body are often about the same length as a microbe. This means that individual and unpredictable interactions between microbes and molecules change how the microbes move. Experimental evidence suggests that microbial transport though such materials could be dominated by direct contact interactions with the individual molecules. Contact interactions are difficult to measure and their effect on locomotion is difficult to quantify. The overall goal of this research is to quantify the effect of direct contact interactions on the propulsion of bacteria. The research will use novel artificial bacteria, 'microrobots', and manufactured mucus to discover which contact interactions dominate transport. The data will improve our ability to understand, perhaps to control, the movement and spread of microorganisms in real-world environments. The investigators will work with local K-12 students in an outreach program named "Move Like a Microbe." The goal of the outreach is to intrigue the students using new understanding of bacterial mobility and encourage them into a science or technology (STEM) path in their later education. Understanding the nanomechanics of microbe transport also will improve our abilities to control disease and understand normal bacterial behavior.Microstructural interactions with swimming microorganisms have mostly been investigated using hydrodynamic and mechanical models. There has been no in-depth examination of the role of contact interactions mediated by electrostatic forces, van der Waals attraction, and biochemical bonding. This research will advance understanding of bacterial transport by combining new microrobotic artificial bacteria systems and a novel semisynthetic mucus to allow well-controlled and well-characterized experiments. The artificial models allow control of density, stiffness, surface charge, surface chemistry, and micromechanical properties, to clarify the relative importance of hydrodynamic, close-range, and nanoscale contact interactions for microbial transport through biological media. Numerical modeling will be used to integrate the interactions into quantitative models of transport. Finally, natural bacteria will be observed moving through well-defined biomaterials and their behavior will be correlated with that observed in the artificial systems, in order to identify which contact interactions are most important for biologically relevant scenarios, testing the hypothesis that contact interactions dominate the effect of organism-scale microstructure on bacterial swimming.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.