A new strategy for creating hybrid materials, part synthetic polymer, part natural protein, has been devised by US researchers. The team at the University of California, Berkeley, used NMR to monitor progress and suggest that such hybrids could exploit the benefits of both components in a wide range of novel applications.

UCB chemists Aaron Esser-Kahn and Matthew Francis, writing in the journal Angewandte Chemie explain how they have been able to fuse the specific biological functions of proteins with the simple bulk and processing properties of polymers. Such polymer-protein hybrids, they say, could be used in developing new chemical sensors, as potentially highly-targeted drug-delivery systems, or even as the components of a future nanomachine.

The team is the first to successfully synthesize a green-fluorescing biodegradable gel that responds to changes in pH and temperature.

Early attempts at protein-polymer hybrids often foundered because the very specific coupling techniques being used were unable to cope with certain protein side-chains. The UCB team, however, believe they have found an approach that will be broadly applicable because in principle it can operate on any protein. Specifically, the team has focused on the carboxy and amino ends of the protein chain, rather than side groups. All proteins are composed of amino acids, in one sense hybrid monomers themselves, part amine, part carboxylic acid. The protein is built up by coupling amino acids in a chain head to tail, amine to acid, which usually means one end of the protein chain is terminated with an amino group and the other with a carboxy group.

The team reasoned that two parallel but mutually independent (orthogonal) reactions would be needed to activate each end of a protein chain. These activated ends would then be hooked on to special "anchor points" on the polymer chain. The result is that individual polymer chains become cross-linked via strands of protein to form an entangled three-dimensional network of protein and polymer. This solid, gelatinous mass, a hydrogel, also incorporates water molecules. A well-known example of a hydrogel formed through a different process, using only synthetic polymers, is the material used to make soft contact lenses.

However, in the UCB hybrid hydrogel, the cross-linking of the polymer chains is exclusively down to the proteins bridges formed between them. The researchers point out that because proteins can be broken down by the protease enzymes used by microbes for digestion, their hydrogels are biodegradable.

The most intriguing aspect of the new hybrid hydrogels created by Francis and Esser-Kahn, however, is the fact that they chose to use a protein that fluoresces green to cross-link their polymer chains, eGFP (enhanced green fluorescent protein). Even after cross-linking occurs, the team found that the green fluorescent protein maintains its active folded state, albeit anchored at each end to polymer molecules. This factor means that the protein can still fluoresce, and so can endow the entire hybrid gel with an eerie green glow under the right conditions.

The team has now demonstrated that the retained green fluorescence of the protein is dependent on pH, which means that the hybrid fluoresces differently when pH changes. Indeed, it fluoresces only in alkali conditions and even slight acidity quenches its glow. The team also demonstrated that raising the temperature also affects the gel. Above 70 Celsius, the protein denatures, its active folded shape is distorted, and this means it can no longer fluoresce, concurrently, the denaturation process excludes water, shortens the cross links and causes the gel to shrink.

"By combining proteins and polymers in this manner we were able to create a bulk material imbued with some of the properties of a protein," the researchers explain, "As the chemistry is independent of amino acid sequence, this method should serve as a general route to a wider number of protein-based materials, each providing a unique function in the resulting gel." p>

Related links:

• Angew Chem Int Edn, 2008, in press
• Group page 
• Francis page

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.