Collaborative Research: Multiscale Analysis and Simulation of Biofilm Mechanics

曾经被认为是单独生活的细菌，现在被认为是相互交流的，生活在被称为生物膜的活跃的微生物群落中。生物膜会导致严重的问题，包括医疗感染、污染和工业应用中的堵塞。相比之下，生物膜在废水处理和微生物燃料电池中发挥着有益的作用。科学家们已经能够表征生物膜的化学成分，但还不知道如何从这些成分及其相互作用中产生一种活性的、自我再生的和自我修复的材料。科学家如何利用他们丰富的人造聚合物知识来了解这些天然聚合物？在细菌构建生物膜群落的过程中，是否有新的物理机制有待发现？为了回答这些问题，该项目旨在通过整合最先进的机械测量、单细胞成像和计算机模拟，揭示生物膜如何从其单个组件中获得机械特性的秘密。通过这些基础研究，科学家们可以设计出更好的策略，要么消除有害的生物膜，要么利用有益的生物膜来创造有用的结构。通过整合多个学科，该项目将培养生物、物理、材料科学和工程领域的多样化学生，为下一代劳动力做好准备。该项目的教育目标将通过课程开发、本科生研究机会和K-12外展计划来实现，并特别努力让代表性不足的学生参与进来。技术概述：生物膜是附着在细胞外聚合物（eps）基质上的细菌群落。该项目的总体目标是整合最先进的机械测量、单细胞成像、诱变、计算机模拟和软物质理论，以解决细菌细胞如何在不同的时间和长度尺度上建立具有新兴机械特性的群落。具体来说，三个研究目标是：(i)将EPS建立为由基质蛋白交联的结合聚合物，（ii）揭示细菌细胞对生物膜力学的贡献，以及（iii）在单细胞水平上测量生物膜力学的发展和异质性。这些目标是通过涉及流变学测试、高分辨率成像、蛋白质生物化学、细菌遗传学和多尺度建模的实验来实现的。这项工作的更广泛的影响是，通过将本项目中涉及的核心概念纳入教育和推广活动，使学生接触和参与生物学、材料科学、物理学和工程学，帮助培养多样化的stem能力的劳动力。教育和推广活动以以下三个目标为中心：(i)为当地高中生扩展科学之路计划，（ii）将研究成果纳入本科和研究生课程，以及（iii）为代表性不足的少数民族学生提供研究经验。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。

NON-TECHNICAL SUMMARYOnce thought to live as solitary units, bacteria are now known to communicate with each other and live in lively microbial communities called biofilms. Biofilms can cause severe problems, including medical infections, fouling, and clogging in industrial applications. In contrast, biofilms play beneficial roles in wastewater treatment and microbial fuel cells. Scientists have been able to characterize the chemical components of biofilms but don’t know yet how an active, self-renewable, and self-healing material emerges from these components and their interactions. How can scientists use their vast knowledge of man-made polymers to understand these natural polymers? Are there new physical mechanisms to be discovered in the way bacteria build their biofilm communities? To answer these questions, this project aims to reveal the secrets of how biofilms derive mechanical properties from their individual components by integrating state-of-the-art mechanical measurement, single-cell imaging, and computer simulations. Through these fundamental studies, scientists can design better strategies that either eliminate harmful biofilms or use beneficial biofilms to create useful structures. By integrating multiple disciplines, this project will train a diverse group of students in the areas of biology, physics, materials science, and engineering, and prepare them for the next-generation workforce. The educational objectives of the project will be realized through curriculum development, undergraduate research opportunities, and K-12 outreach programs, with special efforts to involve underrepresented students.TECHNICAL SUMMARYBiofilms are surface-attached communities of bacteria embedded in a matrix made of extracellular polymeric substances (EPSs). The overarching goal of this project is to integrate state-of-the-art mechanical measurement, single-cell imaging, mutagenesis, computer simulations, and soft matter theory to address how, at different time and length scales, bacterial cells build communities with emerging mechanical properties. Specifically, the three research objectives are to (i) establish EPS as associative polymers crosslinked by matrix proteins, (ii) reveal the contribution of bacterial cells to biofilm mechanics, and (iii) measure the development of biofilm mechanics and heterogeneity at the single-cell level. These objectives are accomplished via experiments involving rheological testing, high-resolution imaging, protein biochemistry, bacterial genetics, and multiscale modeling. The broader impacts of this work are to help produce a diverse STEM-capable workforce by incorporating central concepts addressed in this project into education and outreach activities that expose and engage students in biology, materials science, physics, and engineering. The education and outreach activities center on the following three objectives: (i) expanding the Pathways to Science program for local high school students, (ii) incorporating research findings into the curriculum for both undergraduate and graduate courses, and (iii) providing research experiences to underrepresented minority students.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.