Structure-Interaction Relationship of Polymyxins with the Membrane of Human Kidney Proximal Tubular Cells.

Multidrug-resistant Gram-negative bacteria are a serious global threat to human health. Polymyxins are increasingly used in patients as a last-line therapy to treat infections caused by these life-threatening 'superbugs'. Unfortunately, polymyxin-induced nephrotoxicity is the major dose-limiting factor and understanding its mechanism is crucial for the development of novel, safer polymyxins. Here, we undertook the first all-atom molecular dynamics simulations of the interaction between four naturally occurring polymyxins A1, B1, M1 and colistin A (representative structural variations of the polymyxin core structure) and the membrane of human kidney proximal tubular cells. All polymyxins inserted spontaneously into the hydrophobic region of the membrane where they were retained, although their insertion abilities varied. Polymyxin A1 completely penetrated into the hydrophobic region of the membrane with a unique folded conformation, whereas the other three polymyxins only inserted their fatty acyl tails into this region. Furthermore, local membrane defects and increased water penetration were induced by each polymyxin, which may represent the initial stage of cellular membrane damage. Finally, the structure-interaction relationship of polymyxins was investigated based on atomic interactions at the cell membrane level. The hydrophobicity at positions 6/7 and stereochemistry at position 3 regulated the interactions of polymyxins with the cell membrane. Collectively, our results provide new mechanistic insights into polymyxin-induced nephrotoxicity at the atomic level and will facilitate the development of new-generation polymyxins.

A location- and sharpness-specific tactile electronic skin based on staircase-like nanowire patches.

Human skin can sense an external object in a location-specific manner, simultaneously recognizing whether it is sharp or blunt. Such tactile capability can be achieved in both natural and stretched states. It is impractical to mimic this tactile function of human skin by designing pixelated sensor arrays across our whole curvilinear human body. Here, we report a new tactile electronic skin sensor based on staircase-like vertically aligned gold nanowires (V-AuNWs). With a back-to-back linear or spiral assembly of two staircase structures into a single sensor, we are able to recognize pressure in a highly location-specific manner for both non-stretched and stretched states (up to 50% strain); with a concentric design on the fingertip, we can identify the sharpness of an external object. We believe that our strategy opens up a new route to highly specific second-skin-like tactile sensors for electronic skin (E-skin) applications.

Tattoolike Polyaniline Microparticle-Doped Gold Nanowire Patches as Highly Durable Wearable Sensors.

Wearable and highly sensitive strain sensors are essential components of electronic skin for future biomonitoring and human machine interfaces. Here we report a low-cost yet efficient strategy to dope polyaniline microparticles into gold nanowire (AuNW) films, leading to 10 times enhancement in conductivity and ∼8 times improvement in sensitivity. Simultaneously, tattoolike wearable sensors could be fabricated simply by a direct "draw-on" strategy with a Chinese penbrush. The stretchability of the sensors could be enhanced from 99.7% to 149.6% by designing curved tattoo with different radius of curvatures. We also demonstrated roller coating method to encapusulate AuNWs sensors, exhibiting excellent water resistibility and durability. Because of improved conductivity of our sensors, they can directly interface with existing wireless circuitry, allowing for fabrication of wireless flexion sensors for a human finger-controlled robotic arm system.