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Soft-Bioelectrochemistry for Artificial Respiratory Chain

Periodic Reporting for period 1 - SoftBioArt (Soft-Bioelectrochemistry for Artificial Respiratory Chain)

Período documentado: 2021-11-01 hasta 2023-10-31

The presence of high levels of ROS in the cells of patients with chronic disease is well-known but poorly understood. This is due to a lack of model platforms to detect and evaluate how subtle changes in the cytoplasmic environment affect protein performance in vivo. Methodologies capable of diagnosing how these changes trigger or inhibit a cascade of reactions occurring within cells will inform new strategies to counteract the proliferation of diseases such as breast cancer, acute myeloid leukaemia, and neurodegeneration.
The work performed in SoftBioArt is of paramount importance in medicine and pharmaceutical research since, at the moment, there are no efficient diagnostic methods for the early identification of such chronic diseases. To solve this problem, SoftBioArt will modulate and measure protein responses, activities, aggregation and ROS production at polarised L-L interfaces, showcasing soft-bioelectrochemistry as a new advanced tool for detecting chronic diseases. The SoftBioArt project will explore a new paradigm in the Electron Transport Chain (ETC) by achieving an efficient inter-protein electron transfer at electrified soft-interfaces and using this platform to pinpoint any weak points for possible electron leakage during the ETC. The SoftBioArt program will result in a new platform bringing biomimetic-modified soft-interfaces to a new level to demystify one of the most relevant living machines within mitochondria (respiratory ETC) where any malfunctioning is linked to the development of several chronic human diseases.The SoftBioArt project pushes the boundaries of the current state-of-the-art of bioelectrochemistry at soft-interfaces to determine if this unexplored system can bridge the gap between solid electrode bioelectrochemistry and living systems.
We have demonstrated that aqueous|organic interfaces are suitable and tuneable platforms to carry out bioelectrochemistry and direct electron transfer reactions with proteins in the presence of spectator and co-factor organic molecules, a further step toward full cytoplasmimetics.
SoftBioArt incorporates artificial membranes composed of anionic and neutral phospholipids, inter and trans-membrane proteins and redox molecules assembled at polarisable L-L interfaces mimicking one cell membrane leaflet. One of the advantages of using biphasic aqueous-organic interfaces is that any hydrophobic (transmembrane) or hydrophilic (intermembrane) protein can be solubilised in one phase or another before reaching equilibrium at the interface, thereby removing any protein solubility limitations without adding complicating detergents or emulsifiers. The biphasic systems will be studied with integrated electrochemical, spectroscopic and microscopic technologies able to probe electrified L-L interfaces in situ to achieve a reproducible and controllable biomimetic platform of artificial membranes and bio-systems with successive levels of complexity incorporating proteins involved in mitochondrial respiration.

SoftBioArt's success will yield a new invention patent for a disruptive electrochemical immunoassay platform based on a new generation of organic electronic sensor devices, providing licensing opportunities for the IP with which to establish a new start-up bioelectrochemical sensor company.
Bioelectrochemistry at phospholipid modified aqueous organic interfaces
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