Collaborative Research: Multiscale Analysis and Simulation of Biofilm Mechanics

非技术性总结细菌曾经被认为是孤立的单位，现在人们知道它们可以相互交流，并生活在被称为生物膜的活跃微生物群落中。生物膜可能会导致严重的问题，包括医疗感染、污垢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、自我再生和自我修复的材料。科学家如何利用他们对人造聚合物的广博知识来理解这些天然聚合物？在细菌构建其生物膜群落的方式中是否有新的物理机制被发现？为了回答这些问题，这个项目旨在通过集成最先进的机械测量、单细胞成像和计算机模拟来揭示生物膜如何从它们各自的组件中获得机械性能的秘密。通过这些基础研究，科学家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创建有用的结构。通过整合多个学科，该项目将在生物、物理、材料科学和工程领域培养不同的学生群体，并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推广计划实现，并特别努力让代表性不足的学生参与进来。TECHNICAL SUMMARYBiofilm是嵌入到由胞外聚合物(EPSS)组成的基质中的表面附着的细菌群落。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的机械特性的群落。具体地说，这三个研究目标是(I)建立EPS作为由基质蛋白交联的缔合聚合物，(Ii)揭示细菌细胞对生物膜机制的贡献，以及(Iii)在单细胞水平上测量生物膜机制的发展和异质性。这些目标是通过涉及流变性测试、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。这项工作的更广泛影响是，通过将本项目涉及的中心概念纳入教育和外联活动，帮助培养一支多样化的STEM劳动力队伍，使学生接触和参与生物、材料科学、物理和工程。教育和外展活动围绕以下三个目标：(I)为当地高中生扩大科学之路计划，(Ii)将研究成果纳入本科生和研究生课程，以及(Iii)为未被充分代表的少数族裔学生提供研究经验。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.