Collaborative Research: Using Anisotropic Surface Coating of Nanoparticles to Tune Their Antimicrobial Activity

About This Grant

The rapid rise in antimicrobial/antibiotic resistance in pathogenic bacteria is a global public health threat. Antimicrobial resistance occurs when bacteria and fungi evolve to stop responding to antibiotics and to continue to grow. Each year in the US alone, antimicrobial-resistant bacteria or fungi cause infection in more than 2.8 million people and more than 35,000 deaths. Developing alternatives to traditional antibiotics is critical for addressing this global challenge. This collaborative project supports fundamental research to develop a new type of antimicrobial nanoparticle to combat antibiotic-resistant bacteria. These nanoparticles are unique in that they display a non-uniform coating of hydrophobic and positively charged molecules. Such nanoparticles are expected to act through novel antibiotic mechanisms that are less likely to cause acquired drug resistance in bacteria. The research team will combine experiments with computational modeling to elucidate how interactions of these nanoparticles with bacteria depend on the non-uniform surface chemistry of nanoparticles and the cell wall chemistry of bacteria. The mechanistic understanding from this study will guide the rational design of antimicrobial nanoparticles against a wide range of pathogenic bacteria. By integrating nanoscience research with educational and outreach activities this collaborative project outlines interdisciplinary approaches to promote critical thinking and increase diversity in STEM. These approaches include the development of introductory undergraduate courses that integrate science teaching with art, a collaborative outreach project to K-12 students in rural areas, and training of the next generation of researchers, especially underrepresented minority groups. Developing broad-spectrum antimicrobial nanoparticles is challenging because a single nanoparticle design cannot be a one-size-fits-all solution effective against all bacteria. Instead, nanoparticles whose antimicrobial activity can be tuned to match the bacterial diversity are needed. This collaborative project is focused on developing a new strategy to tune nanoparticle-bacteria interactions by using the anisotropic organization of ligands on nanoparticles. Specifically, experiments will be combined with molecular dynamics simulations to investigate interactions of amphiphilic nanoparticles with model bacterial membranes and a diverse selection of Gram-negative bacterial strains, many of which are resistant to most available antibiotics. The expected results will establish the structure-activity relationship governing the antimicrobial mechanisms of the amphiphilic nanoparticles. Such new understanding will enable the development and optimization of antimicrobial nanoparticles that are potentially more potent than existing ones and whose effects are tunable. The educational and outreach goal of this project is to develop interdisciplinary approaches to promote critical thinking and increase diversity in STEM. These approaches include innovation of introductory undergraduate courses by integrating art with science teaching, a collaborative outreach project to K-12 students in rural areas, and training of next generation of researchers with a particular emphasis on the involvement of underrepresented minority groups. 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.