ON-OFF nanopore: Regulating transmembrane signals with light
A recent study from the Qing, Bayley and Langton groups at Oxford Chemistry introduces a new class of light-controlled nanopores. These “ON-OFF” switchable nanopores, reported in a recent article in Nature Nanotechnology, can be opened and closed using particular wavelengths of light. This allows precise regulation of ionic flow across lipid bilayers.
Robust optical control of ionic communication across membranes will be crucial for advances in synthetic biology. Remote, non-invasive control of chemical and biological processes is often achieved using light-responsive molecular tools. These tools allow researchers to determine precisely where and when processes such as ionic flow across membranes are occurring.
It has been a challenge, however, to design a reversible, light-controlled transmembrane protein channel that completely switches to the desired ON–OFF states while exhibiting a long ON-state lifetime and minimal background current in the OFF-state.
In this study, the team developed photoresponsive nanopores, or ‘photopores’, by covalently modifying the α-hemolysin protein nanopore with arylazopyrazole photoswitches. The photopores were embedded in a membrane and showed reversible, quantitative switching between ON and OFF states in response to two different wavelengths of light (365 nm and 530 nm). After exposure to light, the photopores maintained a long ON-state lifetime (>10 days), with minimal ionic flow in the OFF-state (<5% of the ON state). Furthermore, the photopores can participate in versatile iontronic functions such as switchable iontronic diodes (ionic current rectification) and variable resistors. These properties make the photopores ideal components for constructing smart, soft biomaterials with light and voltage inputs.
The work also demonstrates that exposure to polychromatic light can control the transmembrane ionic flow in a graded manner. In one application of a photopore, the authors showed that sequences of light pulses could be decoded into ionic signals to produce 2D images and text. The work holds significant potential across a variety of fields, including nanotechnology, photochemistry, protein engineering, and synthetic biology.
The lead author of the study, Xingzao Wang, says:
The discovery of photopore fulfilled the longing for a reversible molecular tool to control transmembrane ion flow for synthetic biology. We are excited that the excellent switchable behaviour of photopore was reproducible and consistent at the single-molecule level and ensemble levels. This work holds great promise for a wide range of future biotechnological and engineering applications.
Prof Yujia Qing, corresponding author on the work, commented:
Light-controlled ionic communication is just the beginning. Xingzao's creative work opens up numerous new possibilities. For example, the same principles could be applied to engineer ON/OFF molecular signalling across membranes—an exciting prospect for synthetic biology.
Prof Hagan Bayley, corresponding author on the work, commented:
There are several examples of biological on/off switches in the literature, but most are “leaky”. Xingzao has engineered a protein pore, where off is off and on is on: a marvellous outcome.
Prof Matthew Langton, corresponding author on the work, commented:
This work showcases the power of conjugating molecular photoswitches with proteins to develop highly controllable photo-responsive systems, exemplified here with photo-controllable ion conductance achievable at both single molecule and ensemble levels.
The research was funded by the European Research Council Advanced grant (SYNTISU), and a University of Oxford John Fell Fund (0013248).
For further details, the full publication can be found in Nature Nanotechnology: Wang, X., Kerckhoffs, A., Riexinger, J. et al. "ON–OFF Nanopores for Optical Control of Transmembrane Ionic Communication." Nat. Nanotechnol. (2025). https://doi.org/10.1038/s41565-024-01823-x
