Author : Jared Thomas Wiemann
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.8/5 (417 download)
Book Synopsis Interaction of Amphiphilic Nanoparticles with Model and Bacterial Membranes by : Jared Thomas Wiemann
Download or read book Interaction of Amphiphilic Nanoparticles with Model and Bacterial Membranes written by Jared Thomas Wiemann and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this doctoral work, we aimed to understand how amphiphilic nanoparticles, especially those with anisotropic surface chemistry, interact with biological membranes. Specifically, our overall goal was to elucidate the cytotoxic and antibacterial properties of anisotropic particles relative to amphiphilic nanoparticles with uniform surface chemistry. Nanoparticles with anisotropic surface chemistry have been synthesized for uses in sensing and immunotherapy, among other uses. In our early studies, we evaluated the impact of amphiphilic particles against free-standing biomimetic membranes to assess their potential cytotoxicity. Using "two-faced" amphiphilic Janus nanoparticles, which display separated hydrophobic and hydrophilic sides, we observed that anisotropic surface chemistry enhances the binding of particles to lipid membranes which leads to poration, membrane wrinkling, protrusions, and even collapse of entire membranes. Building upon these findings, we further observed that Janus nanoparticles selectively bind to liquid disordered domains in phase-separated lipid membranes. Extraction of lipids from liquid disordered domains to the hydrophobic nanoparticle hemispheres led to membrane compression and bulging of liquid ordered domains. These studies revealed the distinct consequences of anisotropic amphiphilic nanoparticles on lipid membrane integrity and structure. In the final part of this work, we investigated the antimicrobial properties of amphiphilic Janus nanoparticles. As more multidrug resistant bacteria emerge and fewer antibiotics are developed for clinical use, antibiotic resistance remains an increasing threat to public health. Researchers have since turned to nanomaterials with tailored surface chemistry to evade mechanisms of antibiotic resistance by directly disrupting lipid membranes and cell walls, often times using uniform coatings of cationic or amphiphilic ligands on particle surfaces. Given the potential enhanced antibiotic properties of Janus nanoparticles based on our first works, we fabricated "two-faced" amphiphilic Janus nanoparticles with one hemisphere of the Janus nanoparticles functionalized with hydrophobic alkyl chains and the other hemisphere of the nanoparticles functionalized with either a cationic antibiotic drug, colistin, or a cationic poly(amidoamine) (PAMAM) dendrimer that is not an antibiotic drug. We show that both the colistin/hydrophobic Janus nanoparticles and dendrimer/hydrophobic Janus nanoparticles effectively inhibit the growth of both Gram-negative and Gram-positive bacteria at picomolar concentrations. The half-maximum effective concentrations (EC50) of those cationic/hydrophobic Janus nanoparticles against a variety of bacteria are in the picomolar range and significantly lower than those of conventional nanoparticles with uniform surface chemistry. The Janus nanoparticles inhibit bacterial growth by disrupting bacterial membranes and by inducing reactive oxygen species (ROS). Our results demonstrate that the design of the segregated hydrophobic and cationic charges on the nanoparticle surface is key for their antibiotic potency. The antibiotic potency of the Janus nanoparticles is applicable to cationic ligands and not limited to cationic antibiotic molecules. Those anisotropic amphiphilic Janus nanoparticles are promising new broad-spectrum antibiotic nanoparticles.
