Linking Matrix Composition with Spatially Resolved Mechanical Properties in Polymicrobial Biofilms

该奖项将支持研究了解生物膜的机械和物理特性的机械基础。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上的微生物群落组成的，并被聚合物质包裹着。人们认为这些聚合物质提供了机械稳定性。有害的生物膜通过生物污染或腐蚀船体、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，每年造成数十亿美元的损失。此外，它们占65%的医院感染，影响了1700万人，在美国每年至少造成55万人死亡。相反，有益的生物膜可以清洁水，修复地下水和土壤。尽管生物膜与各种工业、医疗和环境应用具有重要的相关性，但人们对局部生物膜的机械特性是如何由包裹体组成、群落多样性和生物膜物理结构介导的知之甚少。该奖项将支持基础研究，以了解微尺度生物膜的机械特性、包裹性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，包括复杂的环境相关混合培养生物膜。执行该奖项产生的结果将直接为关键应用中管理生物膜的新策略提供信息（例如，在不需要时去除它们，在有益时保留它们），从而显著节省成本。该项目还提供了额外的好处，包括通过对小学、本科和研究生阶段代表性不足的学生进行多学科培训，使美国的STEM劳动力多样化。这项资助将促进我们对暴露于不同环境线索的多微生物生物膜中分子组成、物理结构和机械特性之间的关键但尚未理解的相互关系的理解。迄今为止，关于生物膜机械特性的大部分工作都采用了宏观流变学工具，忽略了生物膜中固有的局部异质性，主要集中在纯培养生物膜（例如单独的铜绿假单胞菌）上，这些生物膜不具有代表性，并且在细胞外聚合物（EPS）组成和机械特性方面可能与医学、环境和工业环境中发现的多微生物生物膜有很大不同。具体来说，研究团队将：1)研究生物膜中的局部结构-组成-粘弹性关系；2)研究生物膜与基质的粘附和内聚特性；3)建立基于均质化的本构模型来预测生物膜的多尺度力学性能。项目结果将首次阐明，EPS成分（如多糖、蛋白质、eDNA）的微尺度变化如何介导双重和混合培养生物膜中剪切模量和粘度、粘附强度和内聚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。这种对空间分解结构/组成-力学性质关系的理解将为生物膜的合理管理和控制提供基础。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。

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.