With the advent of polymyxin B (PmB) resistance in bacteria, the mechanisms for mcr-1 resistance are of crucial importance in the design of novel therapeutics. The mcr-1 phenotype is known to decrease membrane charge and increase membrane packing by modification of the bacterial outer membrane. We used X-ray diffraction, Molecular Dynamics simulations, electrochemistry, and leakage assays to determine the location of PmB in different membranes and assess membrane damage. By varying membrane charge and lipid tail packing independently, we show that increasing membrane surface charge promotes penetration of PmB and membrane damage, whereas increasing lipid packing decreases penetration and damage. The penetration of the PmB molecules is well described by a phenomenological model that relates an attractive electrostatic and a repulsive force opposing insertion due to increased membrane packing. The model applies well to several gram-negative bacterial strains and may be used to predict resistance strength.

What is the most significant result of this study? Post-polymerization methylation of pyridine units within ac onju-gated polymer enabled aswitch in polymer electronics from an initial electron-rich structure to af inal electron-deficient one, without changing polymer length or appreciably affecting polymer confor-mation. The interactions of the nonmethylated (electron-rich) and methylated (electron-deficient) polymers with single-walled carbon nanotubes (SWNTs) were found to be significantly different,t hat is, the electron-rich polymer exclusively dispersed semiconducting SWNTs, while the electron-deficient counterpart exhibited am uch greater tendency to disperse metallic SWNTs. We have, therefore, uncovered ar ational approach for the design of conjugated polymers that enables selective dispersion of carbon nanotubes of aspecific electronic nature. What aspects of this project do you find most exciting? For me, the exciting part of this project is that it uncovers new design principles for imparting selectivity to the polymer-nano-tube interaction. This indicates that certain types of polymers are preferentially attracted to specific carbon nanotubes, based on electron rich/poor characteristics. This allows us to investigate al arge variety of other polymer types, with increasing differences in their electron-rich or-poor character,t oc ontinually improve the degree of selectivity that we have observed in this work. This involves challenges in polymer design, synthesis, characterization, and application. The project also represents as tarting point along ap ath that will ultimately lead to ab etter understanding of the supramolecular polymer-nanotube interaction. What other topics are you working on at the moment? Apart from our work on selective interactions between conjugated polymers and carbon nanotubes, we are investigating an umber of topics involving controlled polymer architectures. We are interested in ways to generate libraries of different conjugated polymers, without changing their average length, through efficient post-poly-merization chemistry.T his not only allows systematic investigation of polymer-nanotube interactions, but also enables the development of new,f unctional polymer structures for applications in ther-apeutics and biosensing. We are also interested in new dendrimer structures for diagnostic imaging, and easily crosslinkable polymers for hydrogel synthesis. Invited for the cover of this issue is the group of Alex Adronov at McMaster University.T he image depicts as tylized view of am etallicc arbon nanotube that is being pulled intos olution, and is related to the findingst hat the electronic nature of ac onjugated polymer has an impact on its selectivity for metallicv ersuss emiconducting single-walled carbon nanotubes, allowingtheir selectivedissolution. Read the full text of the article at

Polymyxin B (PmB) is a "last-line" antibiotic scarcely used due to its nephrotoxicity. However, the molecular basis for antibiotic nephrotoxicity is not clearly understood. We prepared kidney membrane analogs of detergent-susceptible membranes, depleted of cholesterol, and cholesterol enriched, resistant membranes. In both analogs, PmB led to membrane damage. By combining x-ray diffraction, molecular dynamics simulations, and electrochemistry, we present evidence for two populations of PmB molecules: peptides that lie flat on the membranes, and an inserted state. In cholesterol depleted membranes, PmB forms clusters on the membranes leading to an indentation of the bilayers and increase in water permeation. The inserted peptides formed aggregates in the membrane core leading to further structural instabilities and increased water intake. The presence of cholesterol in the resistant membrane analogs led to a significant decrease in membrane damage. Although cholesterol did not inhibit peptide insertion, it minimized peptide clustering and water intake through stabilization of the bilayer structure and suppression of lipid and peptide mobility.

Aerogel films are interesting as coatings due to their unique properties including high surface area, sorption capacity and insulating properties. To date, silica-based aerogel films have been most widely explored due to their ultrahigh surface areas and well-known chemistry. However, the fragile nature of silica aerogels coupled with the limited control over film thickness and dimensions when using traditional deposition techniques limits their use in applications requiring films with good mechanical stability (e.g., in flexible devices). To address these challenges, we present a pressure-aided freeze casting method to pattern, on a variety of substrates (e.g., glass or flexible polyethylene terephthalate), mechanically robust aerogel films composed of covalently cross-linked cellulose nanocrystals (CNCs) with controlled dimensions and internal morphology. To accomplish this, a film of the desired aerogel thickness was deposited on the substrate and a mold with the specific shape for the aerogel was fabricated by xurography (>1 mm lateral dimensions, 7–85 μm thickness) or photolithography (2–500 μm lateral dimensions, 3 μm thickness). An aqueous gel of reactive CNCs or CNCs with poly­(oligoethylene-glycol-methacrylate) was drop cast onto the substrate, and pressure was applied so that the gel adopted the mold shape. The gel was subsequently frozen and lyophilized, and the mold was lifted off the substrate, leaving behind patterned porous aerogel films, which were first explored as cell culture scaffolds. Human prostate cancer cells strongly adhered to the aerogels, where individual cells could be isolated on small aerogel arrays while cell clusters were obtained on larger arrays. This system has potential applications in studying single-cell phenotype and developing miniaturized cell-based assays. The simplicity of this freeze casting and lift-off patterning technique makes it attractive for the fabrication of cellulose-nanocrystal-based aerogels with a variety of compositions for applications requiring materials with high surface area, low density, and good mechanical stability.

Cellulose nanocrystals (CNCs) are rigid rodlike nanoparticles that are derived from natural cellulose. Their high surface area, mechanical strength, and noncytotoxicity have elicited interest in their use for various applications, including composite and construction materials, cosmetic, food, and biomedical products. However, few methods exist to control the morphology and dimensions of assembled CNC structures in the micrometer range. Here, we use water-in-oil droplet microfluidics to template uniform spherical CNC droplets in a nontoxic and sustainable manner. Subsequent evaporation of the water within the droplets promotes the chemical crosslinking of surface-modified CNCs, resulting in ultraporous and flexible micrometer-sized particles. Changing the size of the microfluidic channel or the concentration of the CNC suspension results in microparticles with tunable sizes. The microparticles swell in polar solvents, with larger swelling observed for microparticles fabricated from less-concentrated CNC suspensions. While swelling is pH-independent, it is impacted by ionic strength for microparticles with low cross-link densities. Scanning electron microscopy reveals that the microparticles have macropores and mesopores, supporting a large specific surface area. These porous microparticles have potential for a range of applications, such as drug delivery or sorption agents, or as biodegradable beads for use in cosmetic and food applications.