The Roles of Heterogeneity, Mechanics, and the Environment in Biofilm Growth and Emergent Properties

生物膜是无处不在的附着在表面的细菌群落，它们会污染表面，堵塞管道和过滤设备，从而在工业环境中造成重大问题。然而，生物膜也可以是有益的，例如，在废水处理和微生物群落中。该项目将采用三维成像、基因技术、生物膜特性的机械测量以及生物物理理论和建模，以提供从细胞水平到数千个细胞紧密组织集体的生物膜的统一、多尺度的特征。结果将定义“集体”中出现的属性如何决定生物膜的材料属性。该项目将进一步提供在综合研究框架内进行跨学科培训的机会，在这个框架中，生物、化学、工程和物理的学生和博士后将大量时间花在他们自己的实验室以外的实验室。在这项研究中，三个综合的目的是：(1)探索生物膜生长中行为异质性的起源和后果；(2)从微观尺度(单个细胞或细胞团)到宏观尺度(生物膜)表征生物膜机理；(3)确定环境的物理/化学和力学特征如何影响微观和宏观生物膜特性。重点放在群体感应海洋细菌模型霍乱弧菌上。通过这项研究获得的基本认识将有助于制定生物和工程战略，以促进或阻止相关工业和其他应用环境中细菌生物膜的形成，并通过将微观和环境特征与宏观性质联系起来，可能使新材料的发现和设计成为可能。最后，跨学科的工作将导致在单细胞水平上理解生物膜中的空间和时间基因表达计划，并揭示这些计划如何与环境因素一起决定这些多细胞系统的大规模结构和机械特征。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。

Biofilms are ubiquitous surface-attached bacterial communities that can cause major problems in industrial settings by fouling surfaces and by clogging pipes and filtration devices. However, biofilms can also be beneficial, for instance, in waste-water treatment and in microbiomes. The project will employ three-dimensional imaging, genetic techniques, mechanical measurements of biofilm properties, and biophysical theory and modeling to provide a unified, multi-scale characterization of biofilms that spans from the level of the cell to that of tightly organized collectives of thousands of cells. The results will define how properties that emerge in the "collective" determine the biofilm's material properties. The project will further provide opportunities for interdisciplinary training within an integrated research framework in which students and postdocs from biology, chemistry, engineering, and physics spend significant time in laboratories other than their own. In this research, the three integrated thrusts are: (1) to explore the origins and consequences of behavioral heterogeneity in growing biofilms, (2) to characterize biofilm mechanics from the micro-scale (a single cell or cluster of cells) to the macro-scale (the biofilm), and (3) to determine how physico/chemical and mechanical features of the environment influence microscopic and macroscopic biofilm properties. The focus is on the model quorum-sensing marine bacterium, Vibrio cholerae. The fundamental understanding gained through this research will enable development of biological and engineering strategies to promote or discourage formation of bacterial biofilms in relevant industrial and other applied settings, and, by connecting micro-scale and environmental features to macroscopic properties, may enable the discovery and design of new materials. Finally, the interdisciplinary work will lead to understanding of spatial and temporal gene expression programs in biofilms at the single-cell level and reveal how those programs, in conjunction with environmental factors, dictate the large-scale architectural and mechanical features of these multicellular systems.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.