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We provide a systematic study of the phase diagram and dynamics for single component nanocrystals (NCs) by a combination of self-consistent mean-field molecular theory (MOLT-CF) and molecular dynamics (MD) simulations. 

Biological nanopores are increasingly used in molecular sensing due to their single-molecule sensitivity. The detection of per- and polyfluoroalkyl substances (PFAS) like perfluorooctanoic acid and perfluorooctane sulfonic acid is critical due to their environmental prevalence and toxicity. Here, we investigate selective interactions between PFAS and four cyclodextrin (CD) variants (α-, β-, γ-, and 2-hydroxypropyl-γ-CD) within an α-hemolysin nanopore. We demonstrate that PFAS molecules can be electrochemically sensed by interacting with a γ-CD in a nanopore. Using HP-γ-CDs with increased steric resistance, we can identify homologs of the perfluoroalkyl carboxylic acid and the perfluoroalkyl sulfonic acid families and detect common PFAS in drinking water at 0.4 to 2 parts per million levels, which are further lowered to 400 parts per trillion by sample preconcentration. Molecular dynamics simulations reveal the underlying chemical mechanism of PFAS-CD interactions. These insights pave the way toward nanopore-based in situ detection with promises in environmental protection against PFAS pollution. 

In recent decades, peptide amphiphiles (PAs) have established themselves as promising self-assembling bioinspired materials in a wide range of medical fields. Herein, we report a dual-therapeutic system constituted by an antimicrobial PA and a cylindrical protease inhibitor (LJC) to achieve broad antimicrobial spectrum and to enhance therapeutic efficacy. We studied two strategies: PA–LJC nanostructures (Encapsulation) and PA nanostructures + free LJC (Combination). Computational modeling using a molecular theory for amphiphile self-assembly captures and explains the morphology of PA–LJC nanostructures and the location of encapsulated LJC in agreement with transmission electron microscopy and two-dimensional (2D) NMR observations. The morphology and release profile of PA–LJC assemblies are strongly correlated to the PA:LJC ratio: high LJC loading induces an initial burst release. We then evaluated the antimicrobial activity of our nanosystems toward gram-positive and gram-negative bacteria. We found that theCombinationbroadens the spectrum of LJC, reduces the therapeutic concentrations of both agents, and is not impacted by the inoculum effect. Further, theEncapsulationprovides additional benefits including bypassing water solubility limitations of LJC and modulating the release of this molecule. The different properties of PA–LJC nanostructures results in different killing profiles, and reduced cytotoxicity and hemolytic activity. Meanwhile, details in membrane alterations caused by each strategy were revealed by various microscopy and fluorescent techniques. Last, in vivo studies in larvae treated by theEncapsulationstrategy showed better antimicrobial efficacy than polymyxin B. Collectively, this study established a multifunctional platform using a versatile PA to act as an antibiotic, membrane-penetrating assistant, and slow-release delivery vehicle. 

Abstract The colonization of biomedical surfaces by bacterial biofilms is concerning because these microorganisms display higher antimicrobial resistance in biofilms than in liquid cultures. Developing antimicrobial coatings that can be easily applied to medically‐relevant complex‐shaped objects, such as implants and surgical instruments, is an important and challenging research direction. This work reports the preparation of antibacterial surfaces via the electrodeposition of a conformal hydrogel of self‐assembling cationic peptide‐amphiphiles (PAs). Hydrogels of three PAs are electrodeposited: C₁₆K₂, C₁₆K₃, and C₁₈K₂, where C_nis an alkyl chain ofnmethylene groups and K_mis an oligopeptide ofmlysines. The processing variables (electrodeposition time, potential, pH, salt concentration, agitation) enable fine control of film thickness, demonstrating the flexibility of the method and allowing to unravel the mechanisms underlying electrodeposition. The electrochemically prepared hydrogels inhibit the growth ofStaphylococcus aureus,Escherichia coli, andPseudomonas aeruginosain agar plates, and prevent the formation of biofilms ofAcinetobacter baumanniiandP. aeruginosaand the formation ofA. baumanniicolonies in solid media. C₁₆K₂and C₁₆K₃hydrogels outperform the antimicrobial activity of those of C₁₈K₂while maintaining good compatibility with human cells.