Inspired by the biochemistry of vision, an interdisciplinary team of researchers at the Universities of Manchester, Hull and Bristol have made an artificial molecule that copies the behaviour of a key light-sensitive molecule, rhodopsin.
By taking molecular design features from some antibiotics that can embed into membranes, the researchers built a helical 'foldamer' (a synthetic molecule that mimics a folded biomolecule) that can insert into membranes. They attached a chromophore that can be switched between two structures by different wavelengths of light, and they monitored the changes this causes in the conformation of the foldamer by using 19F NMR spectroscopy. This shows that that the helical foldamer can be switched from favouring 'left-handed' over 'right-handed' versions simply by selecting the wavelength of the light. Even more remarkably, the changes in 'handedness' are transmitted over a distance of up to 2 nanometres. This shows that a folded helical chain can switch its handedness even in a viscous membrane environment.
The work revealed that these artificial structures have similar properties in solution and in membranes, making the prediction of their behaviour much more reliable. It is hoped that this discovery could lead to new ways of building light-sensitive artificial cells and allow scientists to bypass the usual communication mechanisms used by cells.
- The foldamer created in this research is an artificial molecule that mimics the behaviour of rhodopsin, a protein that resides in cell membranes in the retina. The absorption of light by rhodopsin is the first step in the biochemistry of vision.
- A chromophore is a group that absorbs light (and is responsible for the colour of a molecule).
- Helical biomolecules can exist in two 'enantiomeric forms' - meaning that there are two possible molecules with the same chemical composition, but one is the mirror image of the other. Because the helix twists in opposite directions, these are often called 'right-handed' and 'left-handed'. Enantiomers can interact with biological systems in different ways, and this has a huge impact on the chemistry of life.
- The conformational changes were measured by appending fluorine (F) atoms to both the chromophore and at the other end of the foldamer. These F atoms were probed by their nuclear magnetic resonance (NMR) signals, which are very sensitive to chemical environment and so could be used to measure both changes in the handedness of the foldamer, and the speed that it switches between structures upon exposure to light.
The work was supported by the European Research Council (Advanced Investigator Grant ROCOCO) and UK Engineering and Physical Sciences Research Council grants EP/K039547/1 and EP/N009134/1.