ISTM

Prior to taking up his post at Keele, Professor Bashford and his colleagues at the Department of Biochemistry and Immunology at St George’s Hospital Medical School in London used plastic membranes with tiny holes in to investigate how different ions get from one side of the membrane to the other, in order to mimic how ions pass through cell membranes that have been damaged by toxins. Surprisingly, the pores in cell membranes behaved in the same way as the ion channels in nerve membranes. This discovery gave them the opportunity to look at the mechanisms involved when nerves are attacked and provides hope that one day, people with debilitating injuries caused by nerve damage coule be given artificial nerves to help with their recovery.

Twenty years ago, Professor Lindsay Bashford began looking at the damage done to cell membranes by viruses, toxins and other poisons. Previous work by Professor Charles Pasternak found that as certain viruses entered and infected cells, the cell membrane became leaky. Together they discovered that it did not matter whether the attack was by a virus, bee-sting, bacterial toxin or other poison, there was a common pattern - holes were made in the membrane.

The next step was to make a very simple model of the cell membrane - a phospholipid bilayer - in which to investigate the holes made by the toxin chosen for study, in this case S. aureus alpha-toxin. The formation of a toxin-induced hole triggered the flow of ions through the model bilayer in an ‘on'/'off' manner. They found that even in the larger pores formed by certain toxins, the ion current switched between high and low conducting states just like the ion channels of natural membranes.

Researchers from St Petersburg who came to work with the St George’s team then helped to take the research in a new direction. Their links with the Dubna Nuclear Research Institute in Moscow provided access to plastic sheets that might mimic biological membranes. Tiny holes were made in the plastic
membrane and the current through individual pores was measured by pressing a glass microelectrode against the plastic sheet floating on the surface of a suitable solution. This led to the development of a special microscope, based on a glass microelectrode, that has turned out to be very useful for imaging living cells and monitoring the behaviour of their membranes. Using this approach, the current passing through many individual pores was measured under a wide range of conditions. By varying the number of ions on either side of the membrane, they discovered that the current through the pore was virtually independent of the number of ions present outside it.

This observation suggested that a novel mechanism was at work. Each hole filled up with ions - like filling a tube with tennis balls. Then, when a new ion came along and bumped into the top ion in the hole, this popped an ion out the other side, causing a current to flow. This 'knock on' mechanism meant that ions appeared to pass through the hole very quickly, when in fact they are simply joining the queue in the hole.

To see what was going on, the researchers used fluorescent ions and a microscope to demonstrate that the ions did indeed queue in the hole and also to see how the situation changed over time. Their results show that ions flow through the plastic pores by a mechanism similar to that found in nerve cell ion channels.

In the long-term, it is hoped that the understanding of how ions pass through nerve cell membranes, and the fact that plastic membranes can be made to behave in the same way, could lead to the development of artificial nerves. As with a lot of research, other applications may stem from this new understanding. Novel water filtering devices that separate out different ions, or even a green way of generating electricity by passing sea water through the tiny holes in plastic membranes to produce a current, are two of Professor Bashford's ideas.

ISTM Research theme: Neuroscience & Human Metabolism

Development of nanoscale imaging devices using scanning probe technologies.

Research Grants

1983-2002:

Cell Surface Research Fund

1995-1997:

BBSRC: "Flow through, and imaging the aperture of, narrow pores." £134,560

1994-1995:

SERC: "Selective ion flow and ion current switching in narrow pores." £50,000