DNA nanopores as artificial membrane channels for bioprotonics.

Biological membrane channels mediate information exchange between cells and facilitate molecular recognition. While tuning the shape and function of membrane channels for precision molecular sensing via de-novo routes is complex, an even more significant challenge is interfacing membrane channels with electronic devices for signal readout, which results in low efficiency of information transfer - one of the major barriers to the continued development of high-performance bioelectronic devices. To this end, we integrate membrane spanning DNA nanopores with bioprotonic contacts to create programmable, modular, and efficient artificial ion-channel interfaces. Here we show that cholesterol modified DNA nanopores spontaneously and with remarkable affinity span the lipid bilayer formed over the planar bio-protonic electrode surface and mediate proton transport across the bilayer. Using the ability to easily modify DNA nanostructures, we illustrate that this bioprotonic device can be programmed for electronic recognition of biomolecular signals such as presence of Streptavidin and the cardiac biomarker B-type natriuretic peptide, without modifying the biomolecules. We anticipate this robust interface will allow facile electronic measurement and quantification of biomolecules in a multiplexed manner.

L-type calcium channel antagonist isradipine age-dependently decreases plaque associated dystrophic neurites in 5XFAD mouse model.

Epidemiological studies suggest that L-type calcium channel (LTCC) antagonists may reduce the incidence of age-associated neurodegenerative diseases including Alzheimer's disease (AD). However, the neuroprotective mechanism of LTCC antagonists is unknown. Amyloid-ß (Aß) pathology disrupts intracellular calcium signaling, which regulates lysosomes and microglial responses. Neurons near Aß plaques develop dystrophic neurites, which are abnormal swellings that accumulate lysosomes. Further, microglia accumulate around Aß plaques and secrete inflammatory cytokines. We hypothesized that antagonism of LTCCs with isradipine would reduce Aß plaque-associated dystrophic neurites and inflammatory microglia in the 5XFAD mouse model by restoring normal intracellular calcium regulation. To test this hypothesis, we treated 6- and 9-month-old 5XFAD mice with isradipine and tested behavior, examined Aß plaques, microglia, and dystrophic neurites. We found that isradipine treatment age-dependently reduces dystrophic neurites and leads to trending decreases in Aß but does not modulate plaque associated microglia regardless of age. Our findings provide insight into how antagonizing LTCCs alters specific cell types in the Aß plaque environment, providing valuable information for potential treatment targets in future AD studies.