Researchers in the Hunter Group have synthesized molecules that can transmit a signal across a membrane and amplify that signal by triggering a catalytic reaction, mirroring many biological processes.
Signal transduction involves molecules outside a cell signaling to molecules inside the cell that in turn trigger events on the inside. It is an essential feature of biological systems. A small team of researchers in the Hunter Group has created a new and different mechanism for signal transduction by synthesizing molecules that not only transmit a signal across a membrane but also amplify the signal by activating a catalytic reaction on the inside. Group leader Professor Chris Hunter says: “It’s an analogue of what happens in nature to trigger many biological process.”
In biology proteins do the job of bridging the gap between the inside and the outside of a cell. When these proteins bind to molecules in the external environment, they undergo a structural change, which transmits the chemical signal to the inside of the cell, triggering a cascade of catalytic reactions. The Hunter Group used vesicles, which are synthetic cells with just the lipid membrane, and a synthetic molecule that does the job of the protein. “What’s interesting about this work is we can control the molecule’s movement across a membrane. When it sees the signal it drops down through to the other side without actually crossing over. We use pH to drive this molecular machine – high pH pushes the molecule in and turns the catalyst on, low pH pulls it out turning the catalyst off,” said Chris.
A bit like doing the hokey-cokey – pull it out, push it in, shake the cell around – that’s what it’s all about. Clearly, as the subject of a recently published paper in Nature Chemistry, there is a bit more to membrane translocation of a synthetic molecule than an old folk song and dance may suggest. And although there are no immediate applications, this fundamental research represents the first example of an artificial system that is able to transduce and amplify chemical signals across a membrane without physical transfer of matter. Lead author Matthew Langton said: “We are excited by the range of possibilities that could arise from being able to remote-control reactions inside synthetic cells. We are now developing systems that can respond and be controlled by a range of input signals such as small molecules and enzymes, which might ultimately find applications in controlled drug delivery and sensing.”
Chris summed up: “People have been trying to do things like this with synthetic molecules for some time. Molecular machines are generating a lot of excitement in the scientific community. But complex function is difficult to achieve. Our system is an assembly of relatively simple components that reproduces one of the most sophisticated functions of biomolecules. The simplicity of the design means there will be many potential applications.”
IMAGE, ABOVE: Graphic representation showing the behaviour of a synthetic transducer embedded in a lipid bilayer membrane. An input signal (e.g. pH change) leads to the translocation of a molecule embedded in the membrane. In the OFF state (red), the transducer is inactive; when in the ON state (green), the exposure of the transducer to the internal aqueous phase turns over an encapsulated substrate (grey spheres) to generate an output signal (yellow spheres).
Reference:
Matthew J. Langton et al.,‘Controlled membrane translocation provides a mechanism for signal transduction and amplification,’ Nature Chemistry, Dec 2016 DOI:10.1038/NCHEM.2678