RESUMEN
One of the primary global health concerns is the increase in antimicrobial resistance. Polymer chemistry enables the preparation of macromolecules with hydrophobic and cationic side chains that kill bacteria by destabilizing their membranes. In the current study, macromolecules are prepared by radical copolymerization of caffeine methacrylate as the hydrophobic monomer and cationic- or zwitterionic-methacrylate monomers. The synthesized copolymers bearing tert-butyl-protected carboxybetaine as cationic side chains showed antibacterial activity toward Gram-positive bacteria (S. aureus) and Gram-negative bacteria (E. coli). By tuning the hydrophobic content, we prepared copolymers with optimal antibacterial activity against S. aureus, including methicillin-resistant clinical isolates. Moreover, the caffeine-cationic copolymers presented good biocompatibility in a mouse embryonic fibroblast cell line, NIH 3T3, and hemocompatibility with erythrocytes even at high hydrophobic monomer content (30-50%). Therefore, incorporating caffeine and introducing tert-butyl-protected carboxybetaine as a quaternary cation in polymers could be a novel strategy to combat bacteria.
RESUMEN
Bending of double-stranded DNA (dsDNA) has important applications in biology and engineering, but measurement of DNA bend angles is notoriously difficult and rarely dynamic. Here we introduce a nanoscale instrument that makes dynamic measurement of the bend in short dsDNAs easy enough to be routine. The instrument works by embedding the ends of a dsDNA in stiff, fluorescently labeled DNA nanotubes, thereby mechanically magnifying their orientations. The DNA nanotubes are readily confined to a plane and imaged while freely diffusing. Single-molecule bend angles are rapidly and reliably extracted from the images by a neural network. We find that angular variance across a population increases with dsDNA length, as predicted by the worm-like chain model, although individual distributions can differ significantly from one another. For dsDNAs with phased A6-tracts, we measure an intrinsic bend of 17 ± 1° per A6-tract, consistent with other methods, and a length-dependent angular variance that indicates A6-tracts are (80 ± 30)% stiffer than generic dsDNA.
