Peptides are the smallest fragments of proteins, comprised of a few amino acid modules. Like proteins themselves, they have evolved specialist functions including antimicrobial, signalling and hormonal activity.
The EU-funded BISON project, supported by the European Research Council, has explored the smallest possible self-organising peptide arrangement able to display physical properties of interest for a range of functional applications, including bio-based electronics.
“Our well-ordered assemblies, stable at high temperatures, help bring the age of organic electronics closer. This field is in its infancy and our results are already helping to shape it,” says project coordinator Ehud Gazit from Tel Aviv University, the project host.
Exploring peptide characteristics
Focusing on assemblies of peptides comprising only two or three amino acids, the BISON team used X-ray crystallography to characterise the peptide self-assembly process. Additionally, a microfluidics platform was used to demonstrate, for the first time, the expansion and contraction of peptide nanostructures, offering insights into their physical changes.
The team have also used electron microscopy, atomic force microscopy, spectrometry and spectroscopy – complemented by computational techniques – to study the self-assembly of the peptide building blocks in real time.
This led to a number of groundbreaking discoveries, such as the highest quantum yield (efficiency of light emission) yet reported for peptide assemblies. Inspired by this, the team developed microspherical antennae able to absorb sunlight for artificial photosynthesis, demonstrating peptide nanotechnology’s potential for harvesting and storing energy.
On the medical front, a novel tripeptide that behaves like collagen was discovered. “This was counterintuitive because all other peptides form sheet-like stacked assemblies,” explains Gazit. “Embracing the surprise, we engineered the peptide to make rigid assemblies with high piezoelectrical properties.”
This piezoelectricity – the conversion of mechanical energy into electrical currents – offers huge promise. As most piezoelectric materials are lead-based, they are toxic to the human body, precluding their use in implanted biomedical devices. BISON’s peptide assemblies could convert mechanical energy from bodily movement into electrical energy to safely power medical devices such as pacemakers, insulin pumps and artificial valves.
Assemblies relevant for conductive hydrogels were also identified, resulting in a dipeptide design with the lowest critical gelation concentration (the minimum concentration for which a dissolved substance can make a gel) ever reported. For BISON it was 3 500 times lower than gelatine, at 0.002 wt %. This result opens the door for tissue engineering and regeneration applications.
Crucial for all applications was the discovery that the peptide assemblies remained stable in temperatures over 400 °C. “It is always assumed that bio-inspired materials are inherently unstable, but our assemblies could prove even more stable than inorganic ones,” adds Gazit.
Also key for future applications is the ability to create a variety of structural arrangements. Towards this end the team has designed a tripeptide building block that could form nanowires, nanofibres and nanospheres.
Towards even smaller bio-building blocks
Most of the products developed by the optoelectronic industry use metallic materials which damage the planet, as they cause pollution in their manufacture and extraction, as well as being non-degradable as waste. BISON’s continuing work offers environmentally friendly alternatives that contribute to a greener economy.
To further develop the promising biological applications, the team have already been awarded EU funding for two follow-up proof of concept projects: PiezoGel to improve 3D cell cultures, especially for tissue regeneration, and PepZoSkin to explore the creation of electronic skin.
“The next step is to apply our insights to metabolite nanotechnology, working with even smaller bio-organic molecules such as amino acids, vitamins and nucleobases, combining the power of peptide and DNA nanotechnologies to develop peptide nucleic acid (PNA) technology,” notes Gazit.
The team have partnered with Johannes Kepler University Linz in Austria and the Technion Israel Institute of Technology, to advance the technology towards its commercialisation.