Alan Bassindale's research group at The Open University has been interested in the chemistry of silicon compounds for many years and, more recently, in new ways to control the synthesis and reactions of silicon-oxygen framework cage molecules, such as octa- and dodeca- cage silsesquioxanes. Another fruitful research direction in the last few years has been the application of biological methods and reagents to problems in silicon (and metal) chemistry. For instance, the British team has published the first laboratory examples of enzyme-mediated silicon-oxygen bond making and breaking and is also studying aspects of silica transport in diatoms. 

The present paper is a nice combination of the group's biological interests-using phage display technology-with their interest in silsesquioxanes. The aim was to find a new way of looking at models for protein-silicone interactions, which are important to understand in the context of biomedical devices constructed from silicones. 

"It is difficult to do the direct experiment of looking at silicone-protein interactions for a number of reasons" Bassindale says. "We chose to expose silsesquioxanes with a variety of pendant groups on the silicon-oxygen framework to a phage display library. We were gratified to find that there was a statistically significant difference in the ways that different peptides selectively bound to the range of silsesquioxanes." The team's knowledge of substitution reactions at silicon centres was useful in interpreting the interactions. An example was that the peptides binding to octahydrooctasilsesquioxane (Si₈O₁₂H₈) had an unusually large number of imidazole side chains; many years ago, Bassindale had established that imidazole interacts very strongly with silicon-hydrogen containing compounds.

While the increase in understanding of the interactions between the protein and silicone models that was gained in this work is of importance and may help in designing biomedical devices, the most important finding may actually be a methodological improvement in phage display use, as Bassindale comments. 

"The general phage display method uses a library of phages with dodecapeptide chains peptides expressed on the surface at one end of the phage. The assumption is often made that any binding to a substrate is through the expressed peptides. There are many statistical methods for analysing the significance of the amino acid distributions in the array of binding phages; all of which assume this mode of binding. We were concerned that there could be adventitious binding through the protein coat of the peptide. We added about 10% of the wild type phage, which has no expressed proteins on the coat to the library, and through this were able to differentiate between bound library phages and wild type phages. In some cases, where binding of the library is not very tight, there is competition between the library and wild type phages and both can bind to the substrate. This tells us that in those cases the information gained from amino acid distributions and so on is not reliable as the actual binding may be mostly through the coat protein. We could therefore have confidence when all the wild-type phages were washed away that the binding peptides were binding through the expressed peptides and the statistical results gave a real insight into the modes of binding. We now routinely add wild type phage in binding studies as a negative control."

With the improvements in methodology that Bassindale and others have reported, the already useful phage display technology can become an even more valuable, accurate and rapid means for examining surface-substrate interactions. But another implication of this work is that phage displays can be used easily with polymeric materials to probe surface-peptide interactions. It is hard to think of an example of a material that will not at some stage in its use be exposed to proteins and peptides, so to know how they may interact with specific types of peptides and proteins could be very useful.

For Bassindale, the major challenge remains the design of good experiments to extend the usefulness of phage display methods, "...as these have been around for quite a few years now".