Cascading reactions in artificial cells

Dutch researchers have started performing multi-step reactions inside artificial cells made from enzymes and polymers. Several stages of a complex reaction can be carried out at once in the ’nanoreactors’, which could be very useful for studying natural processes or making compounds to power nanomachinery. 

In nature, cell membranes are made from small phospholipid molecules with a hydrophilic head group and a hydrophobic tail. In aqueous solution, these form spherical structures with head groups pointing out and tails pointing in. Inspired by this process, Roeland Nolte’s group at the Radboud University in Nijmegen, the Netherlands, and colleagues at the University of Twente developed a synthetic polymer that self-assembles in the same way. 

’We are making nanocapsules that are more robust than those made in nature, but also have their inner and outer skins completely covered with catalytically active enzymes that can perform reactions,’ Nolte explained to Chemistry World. 

To demonstrate the process, Nolte’s team linked together a modified enzyme called horseradish peroxidase with polystyrene - forming molecules that spontaneously arranged themselves into enclosed spheres in water. By making the spheres in a solution that already contains other enzymes, these will become trapped inside the capsule, creating a primed reaction chamber. 

’By carefully choosing the enzymes, they can be made to work together to perform cascade reactions,’ Nolte explains. ’In this case, we trapped glucose oxidase enzymes which break down glucose and produce hydrogen peroxide. This immediately reacts with the horseradish peroxidase enzymes that were integrated into the cell membrane.’

Nolte notes that making the capsules is quite efficient, and they are stable enough to sit on a shelf for several months. To break them down, if required, only takes a small temperature increase. 

’This research is highly innovative,’ says Heather Maynard, who works on similar chemistry at the University of California in Los Angeles, US. ’Positional assembly of multiple enzymes presents exciting opportunities to reconstitute, study, and regulate cascade reactions found in nature.’

But the strongest prospects lie in further developing possible cascade reactions. ’In general, the nanoreactor concept has potential for far-reaching applications - such as the one-pot multistep synthesis of industrially important compounds,’ Maynard says. 

Nolte’s team is confident that more enzymes can be added to the solution or membrane, and they already working on this. By increasing the number of enzymes in the system, it would be able to carry out a much longer chain of reactions to form complex and useful products.  

Lewis Brindley