A team of materials scientists in the US have made a nanoscale probe that can be implanted into a cell wall and “eavesdrop” on electrical signals inside cells without damaging the cell wall. They hope this will lead to a better understanding of how cells communicate and respond to medication.

You can read about the research behind the development of the so-called “stealth” probe by engineers at Stanford University in California, in the 8 March ahead of print online issue of the Proceedings of the National Academy of Sciences, PNAS. The study was funded by the US Environmental Protection Agency and NASA.

Dr Nick Melosh, an assistant professor of materials science and engineering in whose lab the research was done, told the media the probe mimics natural gateways in the cell membrane and with modification this key feature might serve as a way to convey medication into the heavily defended environment inside a cell.

The researchers also suggested the probe could offer a new way to attach neural prosthetics, allowing for example an artificial arm to be controlled by chest muscles, or implants in the brain to treat depression.

The probe can eavesdrop on everything that goes on in a cell, from electrical signals for cell-to-cell communication to “digestive rumblings” as they react to medication. The monitoring can last for up to a week, they said.

Currrent methods for probing inside cells are destructive and only last for a few hours before the cell dies.

This is thought to be the first time that an inorganic device has been implanted in a cell wall without damaging it.

The probe is 600 nanometers long, is made of metal-coated silicon and fuses so smoothly with cell membranes in the lab that the researchers gave it the name “stealth” probe. Melosh said that:

“The probes fuse into the membranes spontaneously and form good, strong junctions there.”

In fact they fuse so strongly that they can’t pull them out, he said.

“The membrane will just keep deforming rather than let go of the probes,” added Melosh.

Before the “stealth” probe, methods to implant devices were destructive, he explained. These included ripping holes in cells using suction or applying high voltage to punch holes through the membrances, both of which are so destructive that often the cells don’t survive, giving only a small window of opportunity for observations, particularly of electrical measurements of cell function.

To make the probe easy to insert, Melosh and his co-author, graduate student Benjamin D. Almquist, used a type of protein that occurs naturally inside cell walls where it acts as a gatekeeper that controls molecules coming in and out of the cell.

Inside the membrane surrounding every cell is a hydrophobic zone that acts a barrier to stop molecules escaping through the wall (nearly all molecules inside living organisms are water soluble). The only way in or out is through special protein gateways made of a hydrophobic center bounded by two water soluble, or hydrophilic, layers.

Melosh said that essentially what they did was make an inorganic version of one of these membrane proteins. It sits in the membrane without disrupting it, and:

“Now we can envision using it for doing our own gate keeping,” he added.

Melosh and Almquist adapted nanotechnology from the semiconductor industry to make tiny silicon posts, and then coated their tips with three thin layers of metal: a layer of gold sandwiched between two layers of chromium, mirroring the structure of the natural membrane protein. They coated the gold with carbon molecules to make it water-repellent. They didn’t have to do this with the chromium because it is naturally water-repellent.

Melosh said the hardest part was making the hydrophobic band just a few nanometers thick. There were no existing methods that would allow them to apply such a thin layer to the tip of a probe only 200 nanometers in diameter, so he and Almquist devised a way to deposit the metal as a thin coating.

The thin metal coating of the stealth probe is what gives the researchers access to the electrical signalling inside cells.

That, combined with its stability in the cell wall is likely to be a great help to scientists studying cells that rely on electrical stimulation, such as neurons that send signals throughout the nervous system, from brain, down spinal cord to peripheral nerves and back.

The current way of doing this, called a “patch clamp” is quite crude and you have to apply suction that tears a hole in the cell to get access said Melosh. It is very slow, has to be done one cell at a time, and they are often dead with the hour.

“If the stealth probe will give us a long-term patch clamp, we’ll really be able to get the ability to watch these networks over long periods of time, perhaps up to a week,” he explained.

The ideal scenario would be to devise an access port so you can put things in the cell, take things out, measure electrical currents, and so on, said Melosh.

He said what they have shown with this study is that the stealth probe could be a platform on which to start building such devices.

The next step is to see how well the probe works inside living cells. The researchers have already started working with human red blood cells and cervical cancer cells, plus hamster ovary cells.

“Fusion of biomimetic stealth probes into lipid bilayer cores.”
Benjamin D. Almquist and Nicholas A. Melosh.
PNAS 2010 107 (13) 5815-5820; published ahead of print 8 March 2010.

Source: Stanford University.

Written by: Catharine Paddock, PhD