Establishing the Mechanoselective Adhesion of Microorganisms to Biomaterials

包括导管在内的留置医疗器械是现代医疗保健中不可或缺的工具。然而，在美国，超过四分之一的医疗保健相关感染归因于中心静脉导管相关血流感染和导管相关尿路感染。虽然水凝胶涂层通常应用于导管以改善患者舒适度并降低蛋白质和微生物的非特异性吸附，但缺乏揭示微生物最初粘附于固体表面的原因的系统和基础研究，并且可以为抗生物污染材料的开发提供信息。该项目支持基础研究如何与聚合物凝胶的亲水性配对的机械性能影响微生物的初始附着。除了改善水凝胶聚合物涂层的功能性之外，理解材料-生物界面可以使得能够设计宽范围的水凝胶涂覆的生物医学装置（即，导管、植入物、伤口敷料、隐形眼镜）。这个NSF生物材料项目的一个关键组成部分是其目的是教育，提供研究经验，并在材料科学和合成生物学的新兴界面指导多元化的劳动力。这项活动将为本科生和研究生带来许多新的研究经验，包括针对女性和代表性不足的人群的参与努力，包括针对高中生的教育模块“细菌：自然与工程”。预测生物膜如何响应基底力学的能力是一个悬而未决的问题。该活动将通过将微生物附着与具有不同结构-性质关系的材料库和附着细胞的高通量转录组分析相关联来建立大肠杆菌和金黄色葡萄球菌对聚合物涂层的天然反应。通过系统地合成聚合物凝胶从（i）亲水性聚（乙二醇）二甲基丙烯酸酯，（ii）疏水性聚合物聚二甲基硅氧烷，和（iii）可调共聚物凝胶，我们将确定生物膜形成细胞如何感知和响应凝胶的亲水性和刚度在生物材料应用的相关制度。值得注意的是，我们将通过应用合成生物学方法和大肠杆菌和金黄色葡萄球菌菌株的全基因组文库来阐明生物膜抑制的遗传靶点，该靶点控制细菌在我们的凝胶板上的粘附和增殖，以进行细胞粘附的定量基因型-表型作图。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值进行评估，被认为值得支持和更广泛的影响审查标准。

Indwelling medical devices, including catheters, are indispensable tools in modern healthcare. However, over one-quarter of all healthcare-associated infections in the United States are attributed to central line-associated bloodstream infections and catheter-associated urinary tract infections. While hydrogel coatings are typically applied to catheters to improve patient comfort and lower the nonspecific adsorption of proteins and microorganisms, systematic and fundamental studies that reveal why microbes initially adhere to solid surfaces are lacking and could inform the development of biofouling resistant materials. This project supports fundamental research into how mechanical properties paired with the hydrophilicity of polymer gels impacts the initial attachment of microorganisms. In addition to improving the functionality of antifouling polymer coatings, understanding the materials-biology interface can enable the design of a broad range of hydrogel-coated biomedical devices (i.e., catheters, implants, wound dressings, contact lenses). A key component of this NSF-Biomaterials project is its aim to educate, provide research experiences, and mentor a diverse workforce at the emerging interface of materials science and synthetic biology. Numerous new research experiences for undergraduate and graduate students, including engagement efforts aimed at women and underrepresented populations, will result from this activity, including an educational module for high school students called "Bacteria: Natural versus Engineered".The ability to predict how biofilms respond to substrate mechanics is an open question. This activity will establish the native response of Escherichia coli and Staphylococcus aureus to polymer coatings by correlating microbial attachment to a library of materials with varied structure-property relationships and high-throughput transcriptome analysis of the attached cells. By systematically synthesizing polymer gels from (i) hydrophilic poly(ethylene glycol) dimethacrylate, (ii) hydrophobic polymer polydimethylsiloxane, and (iii) tunable copolymer gels, we will identify how biofilm-forming cells sense and respond to the gels' hydrophilicity and stiffness in relevant regimes for biomaterial applications. Notably, we will elucidate genetic targets for biofilm inhibition that control bacterial adhesion and proliferation on our panel of gels by applying synthetic biology approaches and genome-wide libraries for Escherichia coli and Staphylococcus aureus strains to perform quantitative genotype-phenotype mapping for cellular adhesion to mechano-chemically diverse gel materials.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.