Stretching for reversible enzyme activation

A new kind of biologically inspired nanomaterial that can be chemically turned on and off by mechanical stretching has been devised by French researchers. The material could prove useful for biosensors, tissue engineering, and externally controlled drug delivery, the team suggests. 

In nature, cells have the ability to turn mechanical forces into chemical activity by so-called ’mechanotransductive’ processes. Key to these processes are particular proteins called cryptic site proteins. These proteins are usually inactive because their recognition sites are hidden, but under mechanical stretching, the sites become exposed and the biochemical signalling pathways are activated.    

Now, Philippe Lavalle and colleagues based at a number of institutes in Strasbourg, France, have mimicked this phenomenon by creating a new type of mechanically responsive material using enzymes and polyelectrolyte multi-layered films. ’Our work presents the first example of a synthetic "cryptic-like" system that behaves in a similar way to mechanotransductive processes,’ says Lavalle. 

Although scientists have created similar systems that trigger chemical reactions under force in the past, Lavalle points out that this is ’the first example of a system where such an induction takes place in a reversible manner.’  

The material comprises two film layers. The first layer acts as a micro-container and is loaded with enzymes. This is capped by a second, chemically different layer which works as a mechanically sensitive nanobarrier that ’masks’ the enzymes from a substrate, thereby preventing biocatalysis. However, when this nanobarrier is mechanically stretched, the enzymes are exposed, which kick-starts biocatalytic activity. Returning the nanobarrier film to its unstretched state masks the enzymes once again.    

Matthew Dalby, who researches mechanotransduction at the University of Glasgow, UK, thinks the ability to dynamically control the masking and demasking of the enzymes is an exciting development.  ’This research shows that mechanics could be employed to allow cells to have different mechanotransductive states on the same surface, thereby optimising both cell proliferation and differentiation in potential tissue engineering applications,’ comments Dalby.

The bio-inspired material, however, does not completely imitate natural cryptic site proteins, and this offers new insight into how cryptic site substrates can be synthesised. ’In our system, it is not a conformational change of the enzymes that triggers the catalysis [as with cryptic site proteins], but the unmasking of the enzymes. Our system thus provides a new strategy to create mechanochemical responsive substrates,’ explains Lavalle. 

These substrates may have applications as biosensors which become active under stretching or in micro-fluidic devices where a chemical reaction can be triggered by applying pressure. ’Other applications could involve the induction of biological reactions under stress which could be of interest in tissue engineering or even in implants that are externally controlled for the release of drugs,’ Lavalle suggests. 

In order for this new type of material to be used in sensor applications, the team say that more mechanically robust systems need to be developed, which they are currently researching. ’We are also working on systems which are even more close to cryptic site proteins where it is internal structural changes that will exhibit the active sites. These will be based both on proteins and synthetic molecules,’ adds Lavalle.

James Urquhart