Could magnetic beads a billionth of a metre across one day help to heal bones and anaesthetise without drugs? This seemingly unlikely scenario is one possible outcome of a new project being undertaken by Professor Alicia El Haj and Dr Jon Dobson of the University of Keele's Centre for Science and Technology in Medicine.

Dr Dobson is an expert on biocompatible magnetic nanoparticles, while Professor El Haj's expertise lies in cell and tissue engineering. Combining their two disciplines opens up radical research possibilities. With a Showcase award, they aim to use the nanoparticles to open and close ion channels in cell membranes. If they are successful, their technique could have wide-ranging clinical applications.

Ion channels stud the membranes of all cells. They control the passage of essential ions, such as potassium and calcium - movements involved in an enormous number of biological processes, from fertilisation to nerve conduction. Ion channels open and close in response to a variety of stimuli, such as the binding of hormones or voltage changes across the cell membrane. Those that Professor El Haj and Dr Dobson are interested in respond to mechanical stress.

So where do the magnetic beads come in? "Before now, there hasn't been a way of manipulating ion channels experimentally in vitro," explains Professor El Haj. "Using magnetic particles offers us the chance to do so."

The first step will be to explore how the channels work. "We know very little about the pathway from stimulus (mechanical stress) to opening," points out Professor El Haj. They plan to attach the nanoparticles to the protein that forms the ion channel, then apply a torque to twist the protein - and see what happens to the structure of the channel and the flow of ions.

Professor El Haj and Dr Dobson will work on a specially engineered kidney cell line, on the surface of which are potassium ion channel proteins called TREK-1. The protein has four regions, two pore-forming and two supporting regions, which are connected by protein loops.

The loop on the exterior of the protein has been modified to include a specially designed peptide. The magnetic nanoparticles are coated with antibodies that recognise this chain, and so will attach specifically to the loop region. When a magnetic field is applied, the attractive force on the nanoparticles will drag the exterior loop and deform the ion channel.

The team also hopes to probe very specific regions of the protein channel, by modifying internal portions as well as the exterior loop. Their aim is to tweak each region of the molecule in turn, to see whether they can discover the precise mechanism of opening.

To achieve this would be a breakthrough in itself, but Professor El Haj and Dr Dobson aim to go further. The system may work in a single layer of cells, but will it work in a three-dimensional structure, such as a tissue? Professor El Haj is a leading expert in creating in vitro 'scaffolds' that can be seeded with cells, and these will be used to test the technique. It's a further adventurous leap. "But that's the exciting thing about the Showcase awards. They give us the freedom to explore speculative ideas."

Professor El Haj is, however, confident about the project: "We have a good model, a unique region, and we are confident about getting the antibodies to that region. Because the antibodies are very specific, there will be no 'noise' in the system. We will be sure we are measuring the channel activity."

The Showcase grant lasts for two years, not long to test a novel approach, but enough to assess its potential. "These Showcase grants are an exciting idea - it's often difficult to get other research councils to back speculative projects, and we hope that this will take us to the stage where other funding becomes possible."

The clinical scenario is real, suggests Professor El Haj, even if a very long way off. "In theory, if you can recognise surface antigens in the region of a molecule, you can create antibodies to attach to them and use that therapeutically. The ion channels are involved in anaesthesia, and in many cardiovascular diseases. Imagine being able to control operations with magnets rather than drugs. Or to condition a broken bone before the cast comes off. To target malfunctioning cells in the body, without cutting into it - that's the holy grail of surgery."

See also

• Showcase: Awards for Innovative Research

External links

• Professor Alicia El Haj at the Centre for Science and Technology in Medicine, Keele University: Research interests
• Dr Jon Dobson at the Centre for Science and Technology in Medicine, Keele University: Research interests

Further reading

Recommended by Professor El Haj
Yang Y, Magnay J and El Haj A J (2002). Development of a mechano responsive scaffold for tissue engineering. Biomaterials 23: 2119-2126.

Gu Y, Preston M R, Magnay J, El Haj, A J and Publicover S J (2001). Hormonally-regulated expression of voltage-operated Ca 2+ channels in osteocytic (MLO-Y4) cells. Biochem. and Biophys. Res. Comm., 282: 536-542.

Gu Y, Preston M R, El Haj, Howl J D and Publicover S J (2001). Three types of K+ currents in murine osteocytic cells (MLO-Y4). Bone, 28(1): 29-37.

Peake M A, Cooling L M, Magnay J L and El Haj A J (2000). Regulatory pathways involved in mechanical induction of c-fos gene expression in bone cells. J. Appl. Physiol. Part of the Highlighted Series, 89: 2498-2507

Recommended by Dr Dobson
Dobson J and St Pierre T G (1996). Application of the ferromagnetic transduction model to DC and pulsed magnetic fields: Effects on epileptogenic tissue and implications for cellular phone safety. Biochem. Biophys. Res. Commun., 227: 718-723.

Santra S, Tapec R , Theodoropoulou N, Dobson J, Hebard A and Tan W (2001). Synthesis and characterization of silica-coated iron oxide nanoparticles in microemulsion: The effect of non-ionic surfactants. Langmuir, 17: 2900-2906.

Cartmell S H, Dobson J, Verschueren S and El Haj A (2002). Preliminary analysis of magnetic particle techniques for activating mechanotransduction in bone cells. IEEE Transactions on NanoBioscience. In Press.

Zhu C, Bao G and Wang N (2000). Cell mechanics: mechanical response, cell adhesion, and molecular deformation. Annu. Rev. Biomed. Eng. 2000 (2): 189-226.