Search bioRxiv⌕ Search

Biology subjects

Linthicum, W.

Publications and source records attributed to Linthicum, W..

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↗

DECODING THE MECHANOCHEMISTRY OF NEURITE PLASTICITY

The formation and disruption of synaptic connections during development is a fundamental step in neural circuit formation. Subneuronal structures such as neurites are known to be sensitive to the level of spontaneous neuronal activity but the specifics of how neurotransmitter-induced calcium activity regulates neurite homeostasis are not yet fully understood. In response to stimulation by neurotransmitters such as acetylcholine, calcium responses in cells are mediated the Gq/phospholipase C{beta} (PLC{beta})/ phosphatidylinositol 4,5 bisphosphate (PI(4, 5)P2) signaling pathway. Here, we show that prolonged Gq stimulation results in the retraction of neurites in PC12 cells and rupture of neuronal synapses by modulating membrane tension. To understand the underlying cause, we dissected the behavior of individual components of the Gq/PLC{beta}/PI(4, 5)P2 pathway during retraction, and correlated these to the retraction of the membrane and cytoskeletal elements impacted by calcium signaling. We developed a mathematical model that combines biochemical signaling with membrane tension and cytoskeletal mechanics, to show how signaling events are coupled to retraction velocity, membrane tension and actin dynamics. The coupling between calcium and neurite retraction is shown to be operative in the C. elegans nervous system. This study uncovers a novel mechanochemical connection between the Gq/PLC{beta}/(PI(4, 5)P2 pathway that couples calcium responses with neural plasticity.

biophysics↗