Linking Matrix Composition with Spatially Resolved Mechanical Properties in Polymicrobial Biofilms

该奖项将支持理解生物膜机械和物理特性的机械基础的研究。生物膜是一种柔软的多组分生物材料。它们是由附着在表面并包裹在聚合物中的微生物群落组成的。人们认为这些聚合物提供了机械稳定性。有害的生物膜每年通过生物污损或腐蚀船体、热交换器、水处理和分配基础设施、膜以及食品、石油和饮料行业造成数十亿美元的损失。此外，它们占源自医院的感染的65%，影响了1700万人，每年在美国造成至少55万人死亡。相反，有益的生物膜可以净化水，修复地下水和土壤。尽管生物膜与不同的工业、医疗和环境应用具有重要的相关性，但人们对生物膜的机械性能如何受到围隔组成、群落多样性和生物膜物理结构的影响知之甚少。该奖项将支持基础研究，以了解微尺度生物膜机械性能、围栏和群落组成以及物理结构之间的关系。这项工作将研究日益复杂的生物膜，包括复杂的与环境相关的混合培养生物膜。执行这项裁决所产生的结果将直接为管理关键应用中的生物膜的新战略提供依据(例如，当它们不受欢迎时移除，当它们有益时保留)，从而显著节省成本。该项目提供了更多的好处，包括通过对小学、本科生和研究生水平的代表不足的学生进行多学科培训，使国家的STEM劳动力多样化。这笔赠款将促进我们对暴露在不同环境线索中的多菌生物膜中分子组成、物理结构和机械性能之间关键但知之甚少的相互关系的理解。到目前为止，大多数关于生物膜机械性能的工作都使用了宏观流变学工具，忽略了生物膜固有的局部异质性，主要集中在纯培养生物膜(例如铜绿假单胞菌)上，这些生物膜不能代表医疗、环境和工业环境中发现的多菌生物膜的胞外聚合物(EPS)组成和机械性能，而且可能与之有显著差异。具体地说，研究小组将1)研究生物膜中局部结构-组成-粘弹性特性的关系；2)研究生物膜基质的粘附性和粘聚性；3)开发基于均化的本构模型来预测生物膜的多尺度力学特性。项目结果将首次阐明EPS成分(例如，多糖、蛋白质、EDNA)的微观变化如何调节双重和混合培养生物膜中剪切模数和粘度、粘合强度和粘合断裂能的局部异质性，以及环境线索和微生物种群如何改变这种关系。这种对空间分辨结构/成分-机械性能关系的更好理解将为合理管理和控制生物膜提供基础。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，认为值得支持。

This award will support research to understand the mechanistic underpinnings of biofilm mechanical and physical properties. Biofilms are soft multi-component biological materials. They are made of microbial communities attached to surfaces and encased in polymeric substances. It is thought that these polymeric substances provide mechanical stability. Detrimental biofilms cause billions of dollars per year of damage via biofouling or corrosion of ship hulls, heat exchangers, water treatment and distribution infrastructure, membranes, and in the food, oil, and beverage industries. In addition, they account for 65% of infections that originate in hospitals, affecting 17 million people and causing at least 550,000 deaths annually in the US. Conversely, beneficial biofilms can clean water and remediate groundwater and soil. Despite the crucial relevance of biofilms to diverse industrial, medical, and environmental applications, little is known about how local biofilm mechanical properties are mediated by encasement composition, community diversity, and biofilm physical structure. This award will support fundamental research to understand the relationship between microscale biofilm mechanical properties, encasement and community composition, and physical structure. This work will study biofilms of increasing complexity, including complex environmentally-relevant mixed-culture biofilms. The results generated from executing this award will directly inform new strategies to manage biofilms in critical applications (e.g., remove when they are undesirable, and retain when they are beneficial), leading to significant cost savings. The project provides additional benefits, including diversifying the nation’s STEM workforce through multidisciplinary training for underrepresented students at grade school, undergraduate, and graduate levels.This grant will advance our understanding of critical yet poorly understood interrelationships between molecular composition, physical structure, and mechanical properties in polymicrobial biofilms exposed to disparate environmental cues. The majority of the work to date on biofilm mechanical properties has employed macrorheological tools that neglect the inherent local heterogeneity in biofilms and has focused primarily on pure culture biofilms (e.g., P. aeruginosa alone) that are not representative of, and likely differ significantly in extracellular polymeric substances (EPS) composition and mechanical properties from, polymicrobial biofilms that are found in medical, environmental and industrial settings. Specifically, the research team will, 1) study local structure- composition-viscoelastic property relationships in biofilms; 2) study biofilmsubstratum adhesion and cohesion properties; and 3) develop homogenization-based constitutive models to predict the multi-scale mechanical properties of biofilms. Project results will elucidate, for the first time, how microscale variations in EPS constituents (e.g., polysaccharides, proteins, eDNA) mediate local heterogeneity in shear moduli and viscosity, adhesion strength, and cohesive fracture energy in dual and mixed-culture biofilms, and how environmental cues and microbial populations present modify this relationship. This improved understanding of spatially resolved structure/ composition- mechanical property relationships will provide the basis for rational management and control of biofilms.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.