A group of scientists primarily based at the University of Pennsylvania has successfully coupled olfactory receptor (OR) membrane proteins with carbon nanotubes. The creation of such bio-nanoelectronic interfaces has previously been complicated by the fact that membrane proteins have hydrophobic transmembrane domains (remember the phospholipid bilayer!) that make them difficult to express, purify, and solubilize.
The researchers surmounted this problem by purifying the OR proteins from murine (mouse) cells and solubilizing them into digitonin micelles and self –assembling nanodiscs, which they could then attach via a polyhistidine tag to nanotube transistors already functionalized with nickel-nitrilotriacetic acid. Packaging the proteins into nanodiscs not only allowed precise binding of the protein onto the nanotube, but also extended its useful ex vivo lifespan from around one day to close to 10 weeks (5 days for the micelles), which may make the manufacture and use of such devices more practical.
Though the assembly was a feat in itself, the really interesting part was when the researchers tested the odor-sensing abilities of their nanoelectronic devices. As they describe in ACS Nano:
Our results suggest that the capacity of mORs to bind to nonbiological odorants is preserved when integrated with NT devices, maintaining the mOR’s ability to adapt to new analytes. This system thus has potential for the creation of chemical sensor arrays that would have the flexibility of the biological sense of smell; fabrication of such arrays using existing lithography and liquid spotting methods has already been demonstrated…Vapor response measurements demonstrate that ORs with known odorant sensing properties can be coupled to an electronic device and transfer many of those sensing properties to the device.
Though the research was partly funded by DARPA’s RealNose Project, described previously on these pages, because of its potential applications to creating an artificial nose, the researchers see their work having more immediate medical applications. Since olfactory receptors are a type of G-protein couple receptors (GPCR), which are common drug targets, they see their stabilized nanoelectronic devices as having applications in pharmaceutical research:
Future work exploring additional ORs and other types of GPCRs could help to understand differences between protein-nanotube measurements, heterologous measurements, and in vivo measurements. Conceptually, this opens up a very large domain of intra- and intercellular communication to electronic eavesdropping and could serve as a powerful tool for molecular and cell biology research.
Visit the ACS Nano study page: Biomimetic Chemical Sensors Using Nanoelectronic Readout of Olfactory Receptor Proteins
Flashback: DARPA Nose Competition
