News in Brief
“The probes fuse into the membranes spontaneously and form good, strong junctions there,” Melosh said. The attachment is so strong, he said, “We cannot pull them out. The membrane will just keep deforming rather than let go of the probes.”
“We can basically rip holes in the cells using suction, we can use high voltage to puncture holes in their membranes, both of which are fairly destructive,” he said. “Many of the cells don‘t survive.” That limits the duration of any observations, particularly electrical measurements of cell function.
The key to the probe‘s easy insertion – and the membrane‘s desire to retain it – is that Melosh and Almquist based its design on a type of protein na- turally found in cell walls that acts as a gatekeeper, controlling which molecules are allowed in or out.
A cell membrane is essentially a walled fortress. Within the wall itself is a water-repellant, or hydro- phobic, zone. Since almost all molecules in a living being are water soluble, the hydrophobic region acts as a barrier to keep the molecules from slipping through the cell wall. The only way in or out is via the specialized proteins that form bridges across the membrane.
Those “transmembrane” protein gateways match the architecture of the membrane, with a hydrophobic center section bounded by two water soluble, or hydrophilic, layers.
“What we have done is make an inorganic version of one of those membrane proteins, which sits in the membrane without disrupting it,” Melosh said.
“Now we can envision using it for doing our own
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gate keeping.” To build their probe, Melosh and Almquist appropriated nanofabrication methods
from the semiconductor industry to make tiny
silicon posts, the tips of which they coated with three thin layers of metal – a layer of gold between two of chromium – to match the sandwich structure of the membrane. They then coated the gold band with carbon molecules to render it hydrophobic; the chro- mium bands are naturally hydrophilic.
“Getting that hydrophobic band just a few nanome- ters in thickness was an incredible technical challen- ge,” Melosh said. Applying such a thin layer to the tip of a probe only 200nm in diameter was impossible using existing methods, so he and Almquist devised
a new technique using metal deposition to create
the thin band that was needed.
That carefully applied metal coating on the stealth probe could give researchers electrical access to the inside of a cell, where they might monitor the electri- cal impulses generated by various cellular activities, Melosh said. That, combined with the probe‘s stabili- ty in the membrane, could be a huge asset to studies of certain electrically excitable cells such as neurons, which send signals throughout the brain, spinal cord and other nerves.
A device called a “patch clamp” can be used to monitor those sorts of electrical signals among cells now, Melosh said, but in its current form, it is com- paratively crude.
“You come in with it, touch it to the cell surface, ap- ply suction and tear a hole in the cell to give you ac- cess,” he said. “However, it is a fairly slow procedure that has to be done one cell at a time, and it kills the