30/04/2022
Self-assembled logic circuits created from proteins:
In a proof-of-concept study, researchers have created self-assembled, protein-based circuits that can perform simple logic functions. The work demonstrates that it is possible to create stable digital circuits that take advantage of an electron's properties at quantum scales.
One of the stumbling blocks in creating molecular circuits is that as the circuit size decreases the circuits become unreliable. This is because the electrons needed to create current behave like waves, not particles, at the quantum scale. For example, on a circuit with two wires that are one nanometer apart, the electron can "tunnel" between the two wires and effectively be in both places simultaneously, making it difficult to control the direction of the current. Molecular circuits can mitigate these problems, but single-molecule junctions are short-lived or low-yielding due to challenges associated with fabricating electrodes at that scale.
Since the inception of nanotechnology, scientists have dreamed of the ability to create tiny structures and machines that can manipulate matter at will. For example, to this day much research in the field is driven by the concept of nanomachines or devices (or, more evocatively, “nanorobots”) that can interact with biological or other systems in programmable ways. Such nanostructures could, for example, diagnose and treat disease, synthesize novel materials, harvest and shuttle energy, exert mechanical forces, store and transmit information, or arrange other molecules with atomic precision. Richard Feynman outlined this idea of nanoscience in 1959 in his groundbreaking talk “There’s Plenty of Room at the Bottom,” and generations of chemists, biologists, engineers, and materials scientists have since probed the limits of nanostructure synthesis and function. Not surprisingly, biology has served as one of the most fertile sources of inspiration in this endeavor. Cells are teeming with nanoscale analogs of macroscopic structures and machines, including architectural scaffolds (the cytoskeleton), programmable “robots” and assembly lines for building materials in a controlled and monodisperse manner (the ribosome, non-ribosomal peptide synthesis, and enzyme cascades), motors and other machines for exerting mechanical force (actin, myosin, and focal adhesion complexes), channels and transport mechanisms for controlling the flow of matter (ion channels and endocytosis), structural materials with exceptional strength (spider silk, bone, and nacre), adaptors that can selectively bind to a target in a crowded sea of competing molecules (antibodies and ligand receptors), and both “hardware” and “software” for information processing (DNA and RNA copying and transcription, signaling pathways, and riboswitches). Aside from cells, viruses offer another example of complex biological nanodevices with their ability to enter a cell, bypass the cell’s defense mechanisms, and create new copies of themselves by hijacking the host machinery.
All of these functions, and many others, are mediated either entirely or in part by proteins. Although composed primarily of the 20 canonical amino acids, proteins have a breathtakingly wide range of functions as a result of their complex folds and their ability to hierarchically self-assemble with other proteins, DNA, RNA, carbohydrates, and lipids. This complexity comes at a cost, however, because the relationship between protein sequence and function or assembly is still imperfectly understood. The past few decades have brought remarkable progress in directed protein evolution, de novo computational design, the repurposing of existing biological scaffolds such as viral capsids, and the abstraction of design rules in simplified building blocks such as self-assembling peptides or proteins. However, there is still a need for generating nanostructures with a high degree of programmability and structural control that can capitalize on the enormous power of native protein function both for recapitulating and probing biological systems and for designing new materials that can outpace nature. Specifically, one key unmet challenge is building highly anisotropic structures de novo from proteins, such as a nanoscale machine or robot that can perform a function given an external stimulus. Cells possess many such multi-protein complexes, but the difficulty in predicting even monomeric protein structures means that most assemblies made to date are highly symmetric such as polyhedral cages or extended fiber and sheet assemblies and usually static.
"Our goal was to try and create a molecular circuit that uses tunneling to our advantage, rather than fighting against it," says Ryan Chiechi, associate professor of chemistry at North Carolina State University and co-corresponding author of a paper describing the work.
Chiechi and co-corresponding author Xinkai Qiu of the University of Cambridge built the circuits by first placing two different types of fullerene cages on patterned gold substrates. They then submerged the structure into a solution of photosystem one (PSI), a commonly used chlorophyll protein complex.
The different fullerenes induced PSI proteins to self-assemble on the surface in specific orientations, creating diodes and resistors once top-contacts of the gallium-indium liquid metal eutectic, EGaIn, are printed on top. This process both addresses the drawbacks of single-molecule junctions and preserves molecular-electronic function.
"Where we wanted resistors we patterned one type of fullerene on the electrodes upon which PSI self-assembles, and where we wanted diodes we patterned another type," Chiechi says. "Oriented PSI rectifies current -- meaning it only allows electrons to flow in one direction. By controlling the net orientation in ensembles of PSI, we can dictate how charge flows through them."
The researchers coupled the self-assembled protein ensembles with human-made electrodes and made simple logic circuits that used electron tunneling behavior to modulate the current.
"These proteins scatter the electron wave function, mediating tunneling in ways that are still not completely understood," Chiechi says. "The result is that despite being 10 nanometers thick, this circuit functions at the quantum level, operating in a tunneling regime. And because we are using a group of molecules, rather than single molecules, the structure is stable. We can actually print electrodes on top of these circuits and build devices."
The researchers created simple diode-based AND/OR logic gates from these circuits and incorporated them into pulse modulators, which can encode information by switching one input signal on or off depending on the voltage of another input. The PSI-based logic circuits were able to switch a 3.3 kHz input signal -- which, while not comparable in speed to modern logic circuits, is still one of the fastest molecular logic circuits yet reported.
"This is a proof-of-concept rudimentary logic circuit that relies on both diodes and resistors," Chiechi says. "We've shown here that you can build robust, integrated circuits that work at high frequencies with proteins.
"In terms of immediate utility, these protein-based circuits could lead to the development of electronic devices that enhance, supplant and/or extend the functionality of classical semiconductors."
The research appears in Nature Communications. Co-authors Chiechi and Qiu were formerly at University of Groningen, the Netherlands.
