Mitigation of bacterial adhesion and subsequent biofilm formation is quickly becoming a strategy for the prevention of hospital-acquired infections. We demonstrate a basic strategy for surface modification that combines the ability to control attachment by microbes with the ability to inactivate microbes. The surface consists of two active materials: poly(p-phenylene ethynylene)-based polymers, which can inactivate a wide range of microbes and pathogens, and poly(N-isopropylacrylamide)-based polymers, which can switch between an hydrophobic "capture" state and a hydrophilic "release" state. The combination of these materials creates a surface that can both bind microbes in a switchable way and kill surface-bound microbes efficiently. Considerable earlier work with cationic poly(p-phenylene ethynylene) polyelectrolytes has demonstrated and characterized their antimicrobial properties, including the ability to efficiently destroy or deactivate Gram-negative and Gram-positive bacteria, fungi, and viruses. Similarly, much work has shown (1) that surface-polymerized films of poly(N-isopropylacrylamide) are able to switch their surface thermodynamic properties from a swollen, relatively hydrophilic state at low temperature to a condensed, relatively hydrophobic state at higher temperature, and (2) that this switch can control the binding and/or release of microbes to poly(N-isopropylacrylamide) surfaces. The active surfaces described herein were fabricated by first creating a film of biocidal poly(p-phenylene ethynylene) using layer-by-layer methods, and then conferring switchable adhesion by growing poly(N-isopropylacrylamide) through the poly(p-phenylene ethynylene) layer, using surface-attached polymerization initiators. The resulting multifunctional, complex films were then characterized both physically and functionally. We demonstrate that such films kill and subsequently induce widespread release of Gram-negative and Gram-positive bacteria.

A coarse-grained model for DNA that is intended to function realistically at the level of individual bases is reported. The model is composed of residues with up to eight coarse-grained beads each, which is sufficient for DNA-like base stacking and base-base recognition by hydrogen bonding. The beads interact by means of short-ranged pair potentials and a simple implicit solvent model. Movement is simulated by Brownian dynamics without hydrodynamic coupling. The main stabilizing forces are base stacking and hydrogen bonding, as modified by the effects of solvation. Complementary double-stranded chains of such residues form stable double helices over long runs (~10 μs) at or near room temperature, with structural parameters close to those of B-form DNA. Most mismatched chains or mismatched regions within a complementary molecule melt and become disordered. Long-range fluctuations and elastic properties, as measured by bending and twisting persistence lengths, are close to experimental values. Single-stranded chains are flexible, with transient stretches of free bases in equilibrium with globules stabilized by intrastrand stacking and hydrogen bonding. Model DNAs in covalently closed loops form right- or left-handed supercoils, depending on the sign of overtwist or undertwist. Short stem-loop structures melt at elevated temperatures and reanneal when the temperature is carefully lowered. Overall, most qualitative properties of real DNA arise naturally in the model from local interactions at the base-pair level.

Polymers and oligomers with conjugated phenylene ethynylene or thiophene ethynylene backbones have been shown to be potent antimicrobials. The mechanisms by which they act have been unclear, though AFM imaging of Escherichia coli cells before and after exposure to two such biocides, PPE-Th polymer and EO-OPE-1(C3), shows their effects on cell surface structure. Dried, unexposed E. coli cells could be imaged at resolution high enough to discern the physical structure of the cell surfaces, including individual porin proteins and their distribution on the cell. Exposure to 30 μg/mL PPE-Th polymer caused major cell surface disruption due to either emulsification of the outer membrane or the formation of polymer aggregates or both. In contrast, exposure to 30 μg/mL EO-OPE-1(C3) oligomer did not cause large-scale membrane disruption but did cause apparent reorganization of the surface proteins into linear arrays or protein-lipid-OPE complexes that dominate on a small scale. E. coli cells were also successfully imaged underwater, allowing a real-time AFM image series as cells were exposed to 30 μg/mL EO-OPE-1(C3). Solution exposure caused the cell surfaces to noticeably increase their roughness over time. These results agree with proposed mechanisms for cell killing by PPE-Th and EO-OPE-1(C3) put forth by Wang et al.1 in which PPE-Th kills by large-scale disruption of the outer membrane and EO-OPE-1(C3) kills by membrane reorganization with possible pore formation.

No abstract

No abstract