Surfaces that Selectively Manipulate and Kill Bacteria

选择性操纵和杀死细菌的表面

• 批准号: 0805061
• 负责人: Maria Santore
• 金额: --
• 依托单位: University of Massachusetts Amherst
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0805061&HistoricalAwards=false
• 关键词: Surfaces; Selectively; Manipulate; Kill; Bacteria

ID: MPS/DMR/BMAT(7623) 0805061 PI: Santore, Maria ORG: University of Massachusetts-AmherstTitle: Surfaces that Selectively Manipulate and Kill BacteriaINTELLECTUAL MERIT: This program will develop biomaterial surfaces that selectively manipulate bacteria, controlling their adhesion at a level useful for separations, while discriminating and killing targeted types. The surfaces are designed not to harm mammalian cells or accumulate an overcoat of (dead) bacterial debris that can reduce surface activity and support infection. On the surfaces designed and fabricated in this program, the organization of cationic and hydrophobic groups on copolymer chains within antimicrobial polymer brushes will borrow from the membrane-active facially amphiphilic character of host-defense peptides, part of the innate immune system, which evades bacterial resistance. At the 10-300 nm length scale, these new surfaces will emulate the heterogeneous energy landscapes of cell surfaces where rafts cluster proteinaceous functionality to enhance adhesion and signaling. Nano-clustered (10-50 nm) antimicrobial or adhesive functionalities will be randomly distributed on synthetic surfaces whose underlying sterically repulsive character towards cells and bacteria derives from PEG or zwitterionic brushes. These heterogeneous surfaces distinguish bacteria through differences in dynamic adhesion, sensitive to cell size, shape, local curvature, softness (viscoelasticity), and average and local surface chemistry. Besides enabling sensing and separations, the unique dynamic adhesion signatures (skipping, rolling, sliding, arrest) of different bacterial strains and mammalian cells form the basis for their different exposures to antimicrobial functionality, producing selective antimicrobial action, independent of the molecular-scale design. Activities will include synthesis of surface elements and fabrication of surfaces, the experimental study of the dynamic adhesion and viability of bacteria and mammalian cells on these surfaces, the interpretation of data via semiquantitative physico-chemical treatments, and the development of variable-space maps that summarize selectivity, bacterial motion, and viability in a multidimensional materials parameter space. The latter will facilitate rational surface design in diverse applications from implants to clothing.BROADER IMPACTS: The widespread interest in antimicrobial surfaces is driven by the mounting bacterial resistance to antibiotics. Each year in the US there are 90,000 deaths arising from hospital-acquired infections; of these 50,000 are related to catheter infections. So the effective development of antimicrobial polymeric surfaces could have huge practical implications. This project attacks this problem with innovative thinking and technology. The project offers a multidisciplinary setting in which students will be trained in elements of biology, polymer chemistry, materials science, surface science, adhesion, and biophysics. It is proposed that undergraduate students who have worked on the project will be afforded opportunities for industrial intern experience with relevant companies. Outreach to underrepresented groups will be carried out through participation in the Northeast Alliance for Graduate Education and the Professorate, and K-12 outreach will be carried out in conjunction with the UMass MRSEC.

身份证号：MPS/DMR/BMAT（7623）0805061 PI：Santore，Maria ORG：马萨诸塞大学阿默斯特分校标题：选择性操纵和杀死细菌的表面智力优势：该计划将开发选择性操纵细菌的生物材料表面，将其粘附控制在有利于分离的水平，同时区分和杀死目标类型。表面的设计不会伤害哺乳动物细胞或积累（死）细菌碎片的外套，可以降低表面活性和支持感染。在该计划中设计和制造的表面上，抗菌聚合物刷内共聚物链上的阳离子和疏水基团的组织将借用宿主防御肽的膜活性表面两亲性特征，这是先天免疫系统的一部分，可避免细菌耐药性。在10-300 nm的长度尺度上，这些新表面将模拟细胞表面的异质能量景观，其中筏聚集蛋白质功能以增强粘附和信号传导。纳米簇（10-50 nm）抗微生物或粘合剂官能团将随机分布在合成表面上，其对细胞和细菌的潜在空间排斥特性源自PEG或两性离子刷。这些异质表面通过动态粘附的差异来区分细菌，对细胞大小、形状、局部曲率、柔软度（粘弹性）以及平均和局部表面化学反应敏感。除了实现传感和分离之外，不同细菌菌株和哺乳动物细胞的独特动态粘附特征（跳跃、滚动、滑动、停滞）形成了它们不同暴露于抗微生物功能的基础，产生选择性抗微生物作用，而不依赖于分子尺度设计。活动将包括合成的表面元素和制造的表面，在这些表面上的细菌和哺乳动物细胞的动态粘附力和活力的实验研究，通过半定量的物理化学处理的数据的解释，和发展的可变空间的地图，总结选择性，细菌运动，并在多维材料参数空间的活力。后者将促进从植入物到服装的各种应用中的合理表面设计。更广泛的影响：抗菌表面的广泛兴趣是由细菌对抗生素的耐药性不断增加所驱动的。 在美国，每年有90，000人死于医院获得性感染;其中50，000人与导管感染有关。 因此，有效开发抗菌聚合物表面可能具有巨大的实际意义。 这个项目用创新的思维和技术来解决这个问题。 该项目提供了一个多学科的环境，学生将在生物学，高分子化学，材料科学，表面科学，粘附和生物物理学的元素进行培训。 建议为参与该项目的本科生提供在相关公司实习的机会。 对代表性不足的群体的外联将通过参与东北研究生教育联盟和教授进行，K-12外联将与马萨诸塞大学MRSEC一起进行。