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Extracellular traps (ETs), such as neutrophil extracellular traps, are a physical mesh deployed by immune cells to entrap and constrain pathogens. ETs are immunogenic structures composed of DNA, histones, and an array of variable protein and peptide components. While much attention has been paid to the multifaceted function of these structures, mechanistic studies of ETs remain challenging due to their heterogeneity and complexity. Here, a novel DNA-histone mesostructure (DHM) formed by complexation of DNA and histones into a fibrous mesh is reported. DHMs mirror the DNA-histone structural frame of ETs and offer a facile platform for cell culture studies. It is shown that DHMs are potent activators of dendritic cells and identify both the methylation state of DHMs and physical interaction between dendritic cells and DHMs as key tuning switches for immune stimulation. Overall, the DHM platform provides a new opportunity to study the role of ETs in immune activation and pathophysiology., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Neutrophil extracellular traps (NETs) are decondensed chromatin networks released by neutrophils that can trap and kill pathogens but can also paradoxically promote biofilms. The mechanism of NET functions remains ambiguous, at least in part, due to their complex and variable compositions. To unravel the antimicrobial performance of NETs, a minimalistic NET-like synthetic structure, termed "microwebs," is produced by the sonochemical complexation of DNA and histone. The prepared microwebs have structural similarity to NETs at the nanometer to micrometer dimensions but with well-defined molecular compositions. Microwebs prepared with different DNA to histone ratios show that microwebs trap pathogenic Escherichia coli in a manner similar to NETs when the zeta potential of the microwebs is positive. The DNA nanofiber networks and the bactericidal histone constituting the microwebs inhibit the growth of E. coli. Moreover, microwebs work synergistically with colistin sulfate, a common and a last-resort antibiotic, by targeting the cell envelope of pathogenic bacteria. The synthesis of microwebs enables mechanistic studies not possible with NETs, and it opens new possibilities for constructing biomimetic bacterial microenvironments to better understand and predict physiological pathogen responses., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This paper describes a simple technique for patterning channels on elastomeric substrates, at two distinct scales of depth, through the use of controlled fracture. Control of channel depth is achieved by the careful use of different layers of PDMS, where the thickness and material properties of each layer, as well as the position of the layers relative to one another, dictate the depth of the channels formed. The system created in this work consists of a single 'deep' channel, whose width can be adjusted between the micron- and the nano-scale by the controlled application or removal of a uniaxial strain, and an array of 'shallow' nano-scale channels oriented perpendicular to the 'deep' channel. The utility of this system is demonstrated through the successful capture and linearization of DNA from a dilute solution by executing a two-step 'concentrate-then-linearize' procedure. When the 'deep' channel is in its open state and a voltage is applied across the channel network, an overlapping electric double layer forms within the 'shallow' channel array. This overlapping electric double layer was used to prevent passage of DNA into the 'shallow' channels when the DNA molecules migrate into the junctional region by electrophoresis. Release of the applied strain then allows the 'deep' channel to return to its closed state, reducing the cross-sectional area of this channel from the micro- to the nano-scale. The resulting hydrodynamic flow and nano-confinement effects then combine to efficiently uncoil and trap the DNA in its linearized form. By adopting this strategy, we were able to overcome the entropic barriers associated with capturing and linearizing DNA derived from a dilute solution.