Mechanochemotransduction during cardiomyocyte contraction is mediated by localized nitric oxide signaling.

Cardiomyocytes contract against a mechanical load during each heartbeat, and excessive mechanical stress leads to heart diseases. Using a cell-in-gel system that imposes an afterload during cardiomyocyte contraction, we found that nitric oxide synthase (NOS) was involved in transducing mechanical load to alter Ca(2+) dynamics. In mouse ventricular myocytes, afterload increased the systolic Ca(2+) transient, which enhanced contractility to counter mechanical load but also caused spontaneous Ca(2+) sparks during diastole that could be arrhythmogenic. The increases in the Ca(2+) transient and sparks were attributable to increased ryanodine receptor (RyR) sensitivity because the amount of Ca2(+) in the sarcoplasmic reticulum load was unchanged. Either pharmacological inhibition or genetic deletion of nNOS (or NOS1), but not of eNOS (or NOS3), prevented afterload-induced Ca2(+) sparks. This differential effect may arise from localized NO signaling, arising from the proximity of nNOS to RyR, as determined by super-resolution imaging. Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) also contributed to afterload-induced Ca(2+) sparks. Cardiomyocytes from a mouse model of familial hypertrophic cardiomyopathy exhibited enhanced mechanotransduction and frequent arrhythmogenic Ca(2+) sparks. Inhibiting nNOS and CaMKII, but not NOX2, in cardiomyocytes from this model eliminated the Ca2(+) sparks, suggesting mechanotransduction activated nNOS and CaMKII independently from NOX2. Thus, our data identify nNOS, CaMKII, and NOX2 as key mediators in mechanochemotransduction during cardiac contraction, which provides new therapeutic targets for treating mechanical stress-induced Ca(2+) dysregulation, arrhythmias, and cardiomyopathy.

Direct thermal-UV nanoimprint of an iron-containing organometallic hybrid film.

Direct thermal-UV nanoimprinting of an organometallic hybrid film has been demonstrated to fabricate nanoscale features into a novel organic-inorganic solution containing selected metals. The film can be patterned at low temperature and pressure, and requires only a short processing time. When analyzed by energy dispersion X-ray spectroscopy, the authors observe both organic and metal content in the final patterned features. They have also observed that film thermal stability increases after UV and oxygen plasma treatments, which may lead to devices that perform well across a wide spectrum of temperatures.

Polymeric acrylate-based hybrid films containing lead and iron patterned by UV photo-polymerization.

The development and processing of hybrid inorganic-organic thin film materials plays a critical role in advancing interdisciplinary sciences and device manufacturing. Here we present a novel approach to synthesize and deposit acrylate-containing organic/inorganic hybrid films. The material is based on a chemical solution and includes specifically desired metal dopants that are fully integrated into the backbone of the polymer structure. The film can be deposited by simple spin coating, and we confer photosensitive properties to the material making it directly patterned by traditional UV photolithography techniques. Film thickness, chemical characterization, and wet/dry etching capability of the film are also investigated. We believe this innovative material has the potential to be used in a broad range of applications for electronic, photonic, biology, and other interdisciplinary fields.