Understanding the antimicrobial mechanism of metal nanoparticles using super resolution fluorescence microscopy

点击翻译按钮获取中文摘要

Antibiotic resistance of bacteria has become one of the biggest threats to public health in the United States and all over the world. Among the alternative antimicrobial agents, metal nanoparticles have attracted broad interests and attention due to their capabilities for suppressing the growth of bacteria and killing bacteria. However, the exact mechanisms for the antimicrobial effects of metal nanoparticles remain poorly understood. This project will establish the fundamental mechanisms of the antimicrobial behavior of metal nanoparticles as alternatives to commonly prescribed antibiotics. The research team will develop and use advanced imaging tools and techniques with superior spatial and temporal resolution to investigate the interactions between individual live bacteria and silver nanoparticles and obtain knowledge of silver nanoparticles' antimicrobial effects. Results from this research will provide guiding principles on the design and production of metal nanoparticles for antimicrobial applications in food safety and hospital infection-treatments, thus improving U.S. public health and benefiting society. Furthermore, comprehensive education and outreach activities will be implemented to cultivate the interests of America's next generation of scientists and engineers, and provide them with experience in and knowledge of nanomaterials and their applications. This will reinforce and improve the United States' future competitive strengths in STEM fields.The goal of this research is to obtain a quantitative understanding of the antimicrobial mechanism of silver nanoparticles and their interactions with live bacteria at the single-cell level. This will be accomplished by developing methodologies using super-resolution fluorescence microscopy, which will allow the studies of individual biomolecules (e.g., proteins, DNA, and lipids) and their dynamics with a spatial resolution of 20 nanometers and a temporal resolution of 10-30 milliseconds. The goal of the research will be achieved by (1) identifying the effects of silver nanoparticles on spatial organization and function of nucleoid-associated proteins; (2) quantifying how bacterial membrane is damaged by silver nanoparticles; and (3) measuring the dependence of silver nanoparticles? effectiveness on particle shapes, charges, and surface modifications. The results from super-resolution fluorescence microscopy will be validated and complemented by conventional biological techniques and assays. This research will address the current existing controversies surrounding the antimicrobial mechanisms of metal nanoparticles, which are due in part to the lack of both temporal and spatial resolution on single live bacteria. The result will be a better understanding of the nano-bio interface at the cellular and molecular levels. This research will provide valuable, quantitative information necessary to guide the rational design and fabrication of metal nanoparticles for antimicrobial applications. The methodologies developed in this research are expected to be applicable to other nanostructures and different types of bacteria.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.