NER: Biomimetic Platform for Probing Efficacy of Antimicrobial Agents

ECCS-0709481智能优点：人工细菌细胞膜将被化学组装在有图案的金色表面上。将对蛋白质扩散和由此产生的膜结构进行评估，以验证实验室平台模拟细胞膜的属性。然后，所制备的膜将作为测试平台，研究杀菌蛋白与膜表面之间的相互作用所导致的孔形成。孔的形成将通过离子电流来测量，当形成孔时，离子电流穿过膜。抗菌蛋白的毒性将通过基于细胞的细胞毒性测试来确定，并与电化学性质有关。还将开发阵列形式的膜结构图案化，以高通量研究蛋白质-膜相互作用。更广泛的影响：该项目涉及建造一个实验室平台，用于识别下一代抗生素，以应对细菌对当前抗生素耐药性的增加。蛋白质在细胞表面组装形成的毛孔是在自然条件下杀死细菌细胞而不影响哺乳动物细胞的一种机制。人工细胞膜阵列的开发将使潜在杀菌剂的快速筛选以及跨细胞膜的药物输送机制的研究成为可能。研究生和本科生都将进行研究，以获得跨学科研究方面的高级分析培训。研究活动和成果还将作为研究人员本科课程的案例研究，以培养更多跨学科研究的学生。

ECCS-0709481Intellectual Merit: Artificial bacterial cell membranes are to be chemically assembled on patterned gold surfaces. Protein diffusion and the resulting membrane structures will be evaluated to verify that the laboratory platform mimics properties of cell membranes. The fabricated membranes will then serve as a test platform to study pore formation due to interactions between bactericidal proteins and membrane surfaces. Pore formation will be measured by an ion current that results across the membrane when a pore is formed. The toxicity of antimicrobial proteins will be determined by cell-based cytotoxicity assays and related to electrochemical properties. Patterning of membranes structures in array format will be also be developed for high-throughput studies of protein-membrane interactions. Broader Impacts: This project involves the fabrication of a laboratory platform for use in the identification of the next generation of antibiotics in response to increasing bacterial resistance to current antibiotics. Pore formation due to assembly of proteins on cell surfaces that occurs under natural circumstances is a mechanism for killing bacterial cells while leaving mammalian cells intact. The development of artificial cell membrane arrays will allow for rapid screening of potential bactericidal agents as well as studies of drug delivery mechanisms across cell membranes. Both graduate and undergraduate students will perform research to gain advanced analytical training in interdisciplinary research. The research activities and results will also be used as case studies in the investigators' undergraduate courses in order to educate a larger pool of students in interdisciplinary research.