Synthetic System Responds to Pain Relief Signals

Collaborative research by scientists at Manchester and Bristol has created a synthetic cellular communications system which has successfully recognised signals involved in pain relief.

Lead scientist Dr Simon Webb, School of Chemistry at the University of Manchester, said the breakthrough* could hold the key to altering the way cells respond to pain and other sensations because natural communication pathways could be bypassed. “Cells in living organisms need to communicate with the world around them - and one of the most common ways they do this is by using receptor molecules that span their outer membranes,” said Dr Webb from Manchester’s School of Chemistry. “One important type of receptor responds to external chemical signals, such as hormones, by changing shape which then sends a message to the inside of the cell.”

Dr Webb's Manchester group, in collaboration with Professor Jonathan Clayden's group at the University of Bristol, have now designed and synthesized the first artificial mimic of one of these molecular receptors. The synthetic receptor embeds itself into the membranes of simple cell-like structures known as vesicles and like its natural equivalent, changes shape in response to chemical signals.

The researchers were able to get the synthetic receptor to respond to the natural hormone Leu-Enkephalin, which in humans is involved in pain relief as an ‘agonist’ (ie an agent that causes action). They then succeeded in using another chemical messenger Boc-L-Proline (ie an ‘antagonist’, an agent that blocks the action of the agonist) to switch this response off again.

“The discovery that artificial molecules can respond to chemical signals in this way raises the possibility that the natural communication pathways used by cells could be added to or bypassed,” Dr Webb added.

The research was supported by the European Research Council and the Engineering and Physical Sciences Research Council (EPSRC).

*“Ligand-modulated conformational switching in a fully synthetic membrane-bound receptor” F. G. A. Lister, B. A. F. Le Bailly, S. J. Webb and J. Clayden, Nature Chem. 2017, Advance online publication, doi: 10.1038/nchem.2736