Establishing the Mechanoselective Adhesion of Microorganisms to Biomaterials

建立微生物对生物材料的机械选择性粘附

基本信息

批准号：
1904901
负责人：
Jessica Schiffman
金额：
$ 51.55万
依托单位：
University of Massachusetts Amherst
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2024-12-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1904901&HistoricalAwards=false
关键词：
Establishing Mechanoselective Adhesion Microorganisms Biomaterials

项目摘要

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.

包括导管在内的留置医疗设备是现代医疗保健中必不可少的工具。然而，在美国，超过四分之一的医疗相关感染归因于中枢系相关的血液感染和与导管相关的尿路感染。虽然通常将水凝胶涂料应用于导管，以改善患者舒适性，并降低蛋白质和微生物的非特异性吸附，系统和基本研究，这些研究揭示了为什么微生物最初缺乏固体表面并能够为生物燃料耐药材料的发展提供信息。该项目支持有关机械性能与聚合物凝胶亲水性配对的基础研究，影响了微生物的初始附着。除了提高防染色聚合物涂层的功能外，了解材料生物学界面还可以设计出广泛的水凝胶涂层生物医学设备（即导管，植入物，伤口敷料，隐形眼镜）。该NSF-Biomaterials项目的一个关键组成部分是其旨在在材料科学和合成生物学的新兴界面上教育，提供研究经验，并指导多样化的劳动力。这项活动将为本科和研究生提供的许多新的研究经验，包括针对妇女和代表性不足的人群的参与工作，其中包括一个名为“细菌：自然与工程的高中生教育模块”。能够预测生物膜对基质机制的反应是一个悬而未决的问题。该活性将通过将微生物的附着与材料库相关联，并与结构 - 质体关系以及附着的细胞的高通量转录组分析相关联，将大肠杆菌和金黄色葡萄球菌对聚合物涂层的天然反应。通过系统合成的聚合物凝胶，来自（I）氢化聚（乙二醇）二甲基丙烯酸酯，（ii）疏水聚合物聚合物聚合物聚合二甲基硅氧烷和（iii）可调的共聚物凝胶，我们将如何对生物膜形成对凝胶的影响和相关性的相关性，我们将如何识别生物膜形成的剂量。值得注意的是，我们将通过应用合成生物学方法和全基因组大肠杆菌和葡萄球菌抗性的遗传学抑制遗传靶标，以控制我们的凝胶小组对细菌的粘附和增殖，以对大肠杆菌和全基因组的库进行大肠杆菌和金黄色葡萄球菌菌株，以便在材料中进行定量的基因型 - pphenotquel grogch，以使其对材料进行定量的材料，以绘制材料的材料。 NSF的法定使命，并使用基金会的知识分子优点和更广泛的影响审查标准来评估值得支持。