What if you could design proteins, like those in your own cells, to function like conductive, biodegradable electronic wires that are compatible with electronic components, like transistors?

A University of Bristol-led study, published today in The Proceedings of the National Academy of Sciences (PNAS), explains how that could work. The protein-chain-based “nanowires” for conducting electrons could be compatible with conventional electronic components made from copper or iron, as well as biological machinery.

Broad range of applications

Ultimately, these nanoscale designer wires would have the potential for use in a wide range of applications, like biosensors for the diagnosis of diseases and detection of environmental pollutants, and like catalysts as artificial photosynthetic proteins for green industrial biotechnology to capture solar energy.

“While our designs take inspiration from the protein-based electronic circuits necessary for all life on Earth, they are free from much of the complexity and instability that can prevent the exploitation of their natural equivalents,” explained lead author Ross Anderson, Professor of Biological Chemistry at the University of Bristol. “We can also build to order these minute electronic components, specifying their properties in a way that is not possible with natural proteins.”

The multidisciplinary team used advanced computational tools to design simple building blocks that could be combined into longer, wire-like protein chains for conducting electrons.

The Circuits of Life

The researchers were also able to visualize the structures of these wires using protein X-ray crystallography and electron cryo-microscopy (cryo-EM) techniques, which allow structures to be viewed in the finest detail. Pushing the technical boundaries of cryo-EM, they obtained images of the smallest individual proteins ever studied with this technique.

These minuscule wires, which are one thousandth of the width of the finest human hair, were made completely of natural amino acids and heme molecules (found in proteins such as hemoglobin, which transports oxygen in red blood cells). Harmless bacteria were used for the manufacture, eliminating the need for potentially complex and environmentally damaging procedures commonly used in the production of synthetic molecules.

New electronic circuits

The team studied electron transfer, biomolecular simulation, structural biology and spectroscopy, gaining insight into how electrons flow through natural biological molecules—a fundamental process that underpins cellular respiration and photosynthesis.

The multidisciplinary team also used advanced computational tools to design simple building blocks that could be combined into longer, wire-like protein chains for conducting electrons.

This invention could form the foundation of new electrical circuits for creating tailor-made catalysts for green industrial biotechnology and artificial photosynthetic proteins for capturing solar energy. Further advances are expected as the project, which began last year, progresses, presenting “significant opportunities to help meet the transition to net zero and more sustainable industrial processes,” the researchers say.

This breakthrough was possible thanks to a £4.9 million grant from the Biotechnology and Biological Science Research Council (BBSRC), the UK’s largest bioscience funder. It resulted in a five-year project entitled “The Circuits of Life,” involving the Universities of Bristol, Portsmouth, East Anglia, and University College London.

Citation: Hutchins, G. H., Noble, C. E., Bunzel, H. A., Williams, C., Dubiel, P., Yadav, S. K., Molinaro, P. M., Barringer, R., Blackburn, H., Hardy, B. J., Parnell, A. E., Landau, C., Race, P. R., Oliver, T. A., Koder, R. L., Crump, M. P., Schaffitzel, C., Oliveira, A. S., Mulholland, A. J., . . . Anderson, J. L. (2023). An expandable, modular de novo protein platform for precision redox engineering. Proceedings of the National Academy of Sciences, 120(31), e2306046120. https://doi.org/10.1073/pnas.2306046120 (open-access)

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