Tom Fyles from the University of Victoria spoke to NJC about his approach to mimicking Nature, without copying it, to form working channels in membranes.

1. Please explain, for a non-specialist, the significance of your article. 

We are interested in making artificial examples of channels that occur in Nature. Natural channels perform many essential biochemical functions related to energy and materials storage and handling, environmental sensing, and signaling. We imagine that artificial systems that behave like natural examples will allow us to shift these important biochemical functions into a technological context for applications that will be remote from the biochemical inspiration. For example, a channel triggered by a neurotransmitter suggests that we could make sensors that would be triggered by un-natural species for use in sensors or detectors. By shifting the function, rather than the structure, to the synthetic realm, we expect to leave behind the complexities inherent in natural systems. 

Since we are interested in simplicity, we are focused on simple syntheses. Our paper is based on an appealing design idea that we could self-assemble a defined channel portal within a membrane. We did get some really interesting channels from very simple precursors. Unfortunately, we show quite clearly that the channels do not follow our proposed design but are a new type of channel. 

2. What has motivated you to conduct this work? 

We've been exploring how simple compounds can make ion channels and we have many examples. They all form relatively un-structured channels, so we were looking for a simple synthesis of a well-defined structure. The self-assembly of macrocyclic "squares" has been reported by Fujita, Stang, and many others using metal-ligand coordination chemistry. We were inspired to try and make the same type of self-assembly work within a membrane to act as a portal to a channel.

3. Where do you see this work developing in the future? 

There are two directions. The first is to go back to the original design and fix the naive mistakes we made in this paper so that we can truly test the original idea. The second direction is to probe these very large and stable channels to see if they can be fully or partially blocked by other molecules. If that is possible, then these channels will be a step closer to a sensing application. 

4. Are there any particular challenges facing future research in this area? 

Despite all the artificial channels that we and others have made over the past years, there are still very few examples that show the sophisticated channel-based functions seen in Nature. There are a few examples of channels that are regulated by voltage gradients. The type of triggering by a neurotransmitter that I noted above has not yet been demonstrated in a simple system. There are no examples of the "action potential" that is the basis for nerve action in a completely artificial system. All these functions will make great technologies-but we don't know much about how to do any of them. One important insight (or reminder) from this paper is that membrane energetics can assemble complex structures. If we can learn how to work within that environment, we will be able to get at these complex functions by relatively simple means.