Roadmap on emerging concepts in the physical biology of bacterial biofilms: from surface sensing to community formation.

Bacterial biofilms are communities of bacteria that exist as aggregates that can adhere to surfaces or be free-standing. This complex, social mode of cellular organization is fundamental to the physiology of microbes and often exhibits surprising behavior. Bacterial biofilms are more than the sum of their parts: single-cell behavior has a complex relation to collective community behavior, in a manner perhaps cognate to the complex relation between atomic physics and condensed matter physics. Biofilm microbiology is a relatively young field by biology standards, but it has already attracted intense attention from physicists. Sometimes, this attention takes the form of seeing biofilms as inspiration for new physics. In this roadmap, we highlight the work of those who have taken the opposite strategy: we highlight the work of physicists and physical scientists who use physics to engage fundamental concepts in bacterial biofilm microbiology, including adhesion, sensing, motility, signaling, memory, energy flow, community formation and cooperativity. These contributions are juxtaposed with microbiologists who have made recent important discoveries on bacterial biofilms using state-of-the-art physical methods. The contributions to this roadmap exemplify how well physics and biology can be combined to achieve a new synthesis, rather than just a division of labor.

Antibacterial Activity of Nitrogen-Doped Carbon Dots Enhanced by Atomic Dispersion of Copper.

Antibiotic resistance is an imminent threat to human health, requiring the development of effective alternate antibacterial agents. One such alternative includes nanoparticle (photo)catalysts that are good at producing reactive oxygen species (ROS). Herein, we report the design and preparation of nitrogen-doped carbon dots functionalized with atomically dispersed copper centers by Cu-N coordination (Cu/NCD) that exhibit apparent antibacterial activity toward Gram-negative Escherichia coli (E. coli) under photoirradiation. The growth of E. coli cells is found to be markedly inhibited by Cu/NCD under 365 nm photoirradiation, whereas no apparent inhibition is observed in the dark or with the copper-free carbon dots alone. This is ascribed to the prolonged photoluminescence lifetime of Cu/NCD that facilitates the separation of photogenerated electron-hole pairs and ROS formation. The addition of tert-butyl alcohol is found to completely diminish the antimicrobial activity, suggesting that hydroxyl radicals are responsible for microbial death. Consistent results are obtained from fluorescence microscopic studies using CellROX green as the probe. Similar bactericidal behaviors are observed with Gram-positive Staphylococcus epidermidis (S. epidermidis). The copper content within the carbon material is optimized at a low loading of 1.09 wt %, reducing the possibility of toxic copper-ion leaching. Results from this study highlight the significance of carbon-based nanocomposites with isolated metal species as potent antimicrobial reagents.

Antimicrobial activity of graphene oxide quantum dots: impacts of chemical reduction.

Design and engineering of graphene-based functional nanomaterials for effective antimicrobial applications has been attracting extensive interest. In the present study, graphene oxide quantum dots (GOQDs) were prepared by chemical exfoliation of carbon fibers and exhibited apparent antimicrobial activity. Transmission electron microscopic measurements showed that the lateral length ranged from a few tens to a few hundred nanometers. Upon reduction by sodium borohydride, whereas the UV-vis absorption profile remained largely unchanged, steady-state photoluminescence measurements exhibited a marked blue-shift and increase in intensity of the emission, due to (partial) removal of phenanthroline-like structural defects within the carbon skeletons. Consistent results were obtained in Raman and time-resolved photoluminescence measurements. Interestingly, the samples exhibited apparent, but clearly different, antimicrobial activity against Staphylococcus epidermidis cells. In the dark and under photoirradiation (400 nm), the as-produced GOQDs exhibited markedly higher cytotoxicity than the chemically reduced counterparts, likely because of (i) effective removal by NaBH4 reduction of redox-active phenanthroline-like moieties that interacted with the electron-transport chain of the bacterial cells, and (ii) diminished production of hydroxyl radicals that were potent bactericidal agents after chemical reduction as a result of increased conjugation within the carbon skeletons.

Highly Tunable Hollow Gold Nanospheres: Gaining Size Control and Uniform Galvanic Exchange of Sacrificial Cobalt Boride Scaffolds.

In principle, the diameter and surface plasmon resonance (SPR) frequency of hollow metal nanostructures can be independently adjusted, allowing the formation of targeted photoactivated structures of specific size and optical functionality. Although tunable SPRs have been reported for various systems, the shift in SPR is usually concomitant with a change in particle size. As such, more advanced tunability, including constant diameter with varying SPR or constant SPR with varying diameter, has not been properly achieved experimentally. Herein, we demonstrate this advanced tunability with hollow gold nanospheres (HGNs). HGNs were synthesized through galvanic exchange using cobalt-based nanoparticles (NPs) as sacrificial scaffolds. Co2B NP scaffolds were prepared by sodium borohydride nucleation of aqueous cobalt chloride and characterized using UV-vis, dynamic light scattering, X-ray absorption spectroscopy, and X-ray photoelectron spectroscopy. Careful control over the size of the Co2B scaffold and its galvanic conversion is essential to realize fine control of the resultant HGN diameter and shell thickness. In pursuit of size control, we introduce B(OH)4- (the final product of NaBH4 hydrolysis) as a growth agent to obtain hydrodynamic diameters ranging from ∼17-85 nm with relative standard deviation <3%. The highly monodisperse Co2B NPs were then used as scaffolds for the formation of HGNs. In controlling HGN shell thickness and uniformity, environmental oxygen was shown to affect both the structural and optical properties of the resultant gold shells. With careful control of these key factors, we demonstrate an HGN synthesis that enables independent variation of diameter and shell thickness, and thereby SPR, with unprecedented uniformity. The new synthesis method creates a truly tunable plasmonic nanostructure platform highly desirable for a wide range of applications, including sensing, catalysis, and photothermal therapy.

Photo-enhanced antibacterial activity of ZnO/graphene quantum dot nanocomposites.

Synthesis of new, highly active antibacterial agents has become increasingly important in light of emerging antibiotic resistance. In the present study, ZnO/graphene quantum dot (GQD) nanocomposites were produced by a facile hydrothermal method and characterized by an array of microscopic and spectroscopic measurements, including transmission electron microscopy, X-ray photoelectron spectroscopy, UV-vis and photoluminescence spectroscopy. Antibacterial activity of the ZnO/GQD nanocomposites was evaluated with Escherichia coli within the context of minimum inhibitory concentration and the reduction of the number of bacterial colonies in a standard plate count method, in comparison to those with ZnO and GQD separately. It was found that the activity was markedly enhanced under UV photoirradiation as compared to that in ambient light. This was ascribed to the enhanced generation of reactive oxygen species under UV photoirradiation, with minor contributions from membrane damage, as manifested in electron paramagnetic resonance and fluorescence microscopic measurements. The results highlight the significance of functional nanocomposites based on semiconductor nanoparticles and graphene derivatives in the development of effective bactericidal agents.

Antibacterial mechanisms of graphene-based composite nanomaterials.

Pathogenic bacteria are gaining resistance to conventional antibiotics at an alarming rate due to overuse and rapid transfer of resistance genes between bacterial populations. As bacterial resistance to antibiotics causes millions of fatalities worldwide, it is of urgent importance to develop a new class of antibiotic materials with both broad-spectrum bactericidal activity and suitable biocompatibility. Graphene derivatives are rapidly emerging as an extremely promising class of antimicrobial materials due to their diverse bactericidal mechanisms and relatively low cytotoxicity towards mammalian cells. By combining graphene derivatives with currently utilized antibacterial metal and metal-oxide nanostructures, composite materials with exceptional bactericidal activity can be achieved. In this review, the antibacterial activities of graphene derivatives as well as their metal and metal-oxide composite nanostructures will be presented. The synthetic methodology for these various materials will be briefly mentioned, and emphasis will be placed on the evaluation of their mechanisms of action. This information will provide a valuable insight into the current understanding of the interactions governing the microbial toxicity of graphene-based composite nanostructures.

Thermoswitchable Janus Gold Nanoparticles with Stimuli-Responsive Hydrophilic Polymer Brushes.

Well-defined thermoswitchable Janus gold nanoparticles with stimuli-responsive hydrophilic polymer brushes were fabricated by combining ligand exchange reactions and the Langmuir technique. Stimuli-responsive polydi(ethylene glycol) methyl ether methacrylate was prepared by addition-fragmentation chain-transfer polymerization. The polymer brushes were then anchored onto the nanoparticle surface by interfacial ligand exchange reactions with hexanethiolate-protected gold nanoparticles, leading to the formation of a hydrophilic (polymer) hemisphere and a hydrophobic (hexanethiolate) one. The resulting Janus nanoparticles showed temperature-switchable wettability, hydrophobicity at high temperatures, and hydrophilicity at low temperatures, due to thermally induced conformational transition of the polymer ligands. The results further highlight the importance of interfacial engineering in the deliberate functionalization of nanoparticle materials.