Surfaces that Selectively Manipulate and Kill Bacteria

ID：MPS/DMR/BMAT(7623)0805061 PI：Santore，Maria ORG：马萨诸塞大学阿默斯特分校标题：选择性操纵和杀灭细菌的表面内部优点：该计划将开发选择性地操纵细菌的生物材料表面，将它们的粘附性控制在有助于分离的水平，同时区分和杀死目标类型。这种表面被设计成不会伤害哺乳动物细胞，也不会积聚一层(死亡的)细菌碎片，从而降低表面活性并支持感染。在这个项目中设计和制造的表面上，抗菌聚合物刷子内共聚物链上的阳离子和疏水基团的组织将借鉴宿主防御多肽的膜活性两亲性，这是先天免疫系统的一部分，可以逃避细菌耐药性。在10-300 nm的长度尺度上，这些新的表面将模拟细胞表面的异质能量景观，其中木筏聚集蛋白质功能以增强黏附和信号传递。纳米簇状(10-50 nm)抗菌或粘合功能将随机分布在合成表面上，其潜在的对细胞和细菌的空间排斥特性源于聚乙二醇或两性离子刷子。这些异质表面通过动态黏附、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的不同来区分细菌。除了能够进行传感和分离之外，不同细菌菌株和哺乳动物细胞独特的动态黏附特征(跳过、滚动、滑动、停滞)形成了它们对抗菌功能的不同暴露基础，产生了独立于分子尺度设计的选择性抗菌作用。活动将包括表面元素的合成和表面的制造，对细菌和哺乳动物细胞在这些表面上的动态附着和活性的实验研究，通过半定量的物理化学处理来解释数据，以及开发在多维材料参数空间中总结选择性、细菌运动和活性的可变空间图。后者将有助于在从植入物到服装的各种应用中进行合理的表面设计。BROADER的影响：抗菌表面的广泛兴趣是由于细菌对抗生素的耐药性不断增加所驱动的。在美国，每年有9万人死于医院获得性感染；其中5万人与导管感染有关。因此，抗菌聚合物表面的有效开发具有巨大的现实意义。这个项目用创新的思维和技术解决了这个问题。该项目提供了一个多学科的环境，学生将在其中接受生物学、聚合物化学、材料科学、表面科学、附着力和生物物理学的元素培训。建议曾参与该项目的本科生将获得在相关公司实习的机会。将通过参加东北研究生教育联盟和教授联盟，与任职人数不足的群体开展外联活动，并将与马萨诸塞州大学研究生教育和培训中心一起开展K-12外联活动。

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.