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：选择性操纵和杀死细菌的表面智力优势：该计划将开发生物材料表面，选择性地操纵细菌，控制它们的粘附在一个有利于分离的水平，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，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。在本项目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性基团的组织将借鉴宿主防御肽的膜活性表面两亲性特征，宿主防御肽是先天免疫系统的一部分，可以逃避细菌的耐药性。在10- 300nm的长度范围内，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纳米）抗菌或粘附功能将随机分布在合成表面上，其对细胞和细菌的潜在立体排斥特性来自聚乙二醇或两性离子刷。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）构成了它们不同的抗菌功能暴露的基础，产生选择性的抗菌作用，独立于分子尺度的设计。活动将包括表面元素的合成和表面的制造，细菌和哺乳动物细胞在这些表面上的动态粘附和活力的实验研究，通过半定量的物理化学处理来解释数据，以及在多维材料参数空间中总结选择性，细菌运动和活力的可变空间图的发展。后者将促进从植入物到服装的各种应用中合理的表面设计。更广泛的影响：对抗菌表面的广泛兴趣是由不断增加的细菌对抗生素的耐药性驱动的。美国每年有9万人死于医院获得性感染；其中5万例与导管感染有关。因此，抗菌高分子表面的有效开发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、聚合物化学、材料科学、表面科学、粘附和生物物理学等方面接受训练。建议参与项目的本科生有机会到相关公司进行行业实习。对代表性不足的群体的外展将通过参与东北研究生教育和教授联盟来进行，K-12外展将与马萨诸塞大学MRSEC一起进行。

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.