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Huey, B.

Publications and source records attributed to Huey, B..

2 recordsLinked to original sources

Electrically Conductive DNA-Inspired Coating for Intracortical Neural Microelectrodes

Different from conventional electrodes, intracortical neural microelectrodes are the size of one or several neural cells. Due to the limited space for cell-electrode connections, the bio-integration between each neural cell and the electrode surface is critical. To improve bio-integration and electrode functions, various coating materials (such as conductive polymers (CPs), carbon nanotubes (CNTs), and natural hydrogels) have been developed aiming to provide an enhanced interface for neuron recruitment, bio-anchorage, and electrical function. However, synthetic materials usually have limited biocompatibility and/or relatively high cytotoxicity, while biological materials present poor electrical functions. Therefore, current coatings possess biological, functional or electrochemical limitations that are not optimal for intracortical neural microelectrodes. To overcome this obstacle, we developed an electrically conductive coating based on biological molecules, named Janus base nano-coating (JBNc). JBNc is formed by Janus base nanotubes (JBNts) which are a family of nanotubes assembled from engineered DNA base pair units. Based on the long-distance translocation ability of the {pi} electrons of JBNts, we developed them into an electrically conductive coating on the electrode surface. For the first time, we reported the DNA-inspired JBNc had an electrochemical performance that met and exceeded standard metal electrode surface in cyclic voltammetry, impedance spectroscopy, charge injection capacity tests, and neural recording. Moreover, we demonstrated enhanced bio-anchorage and microelectrode interface integration using SEM and AFM. Importantly, we demonstrated enhanced functional response to JBNc microelectrodes with immunohistochemical staining and RNA sequencing (RNAseq) analysis. Using cell viability assays, we also showed the benefits of DNA-mimicking chemistry of Janus base nanomaterials compared to conventional microelectrode coatings. We anticipate that these results will serve as a foundation for the continued development and study of JBNc to enhance interface dynamics and ultimately the performance and reliability of brain microelectrodes.

bioengineering↗

A contraction stress model of hypertrophic cardiomyopathy due to thick filament sarcomere mutations

Thick filament sarcomere mutations are the most common cause of hypertrophic cardiomyopathy (HCM), a disorder of heart muscle thickening associated with sudden cardiac death and heart failure, with unclear mechanisms. We engineered an isogenic panel of four human HCM induced pluripotent stem cell (iPSc) models using CRISPR/Cas9, and studied iPSc-derived cardiomyocytes (iCMs) in 3-dimensional cardiac microtissue (CMT) assays that resemble in vivo cardiac architecture and biomechanics. HCM mutations result in hypercontractility in association with prolonged relaxation kinetics in proportion to mutation pathogenicity but not calcium dysregulation. RNA sequencing and protein expression studies identified that HCM mutations result in p53 activation secondary to increased oxidative stress, which results in increased cytotoxicity that can be reversed by p53 genetic ablation. Our findings implicate hypercontractility as an early consequence of thick filament mutations, and the p53 pathway as a molecular marker and candidate therapeutic target for thick filament HCM.

cell biology↗