Tight squeeze forces cells to take their medicine

Douglas Heaven, reporter

(Image: Emily Jackson and Armon Sharei/Jensen and Langer Group)

A short sharp squash in these channels and a cell's normally impregnable membrane pops open - good news when you want to slip a molecule or nanoparticle of your choice in there.

Getting stuff into cells is difficult, fortunately - the outer membrane protects a cell from natural intruders. Annoyingly, it is also a barrier for drug molecules, or for nanoparticles used in some imaging techniques. One way around this is to use viruses or proteins - both of which have developed their own clever ways of entering a cell - to deliver the desired payload. But this can be inefficient and has drawbacks, especially when deliberately introducing a virus into a cell.

Armon Sharei at the Massachusetts Institute of Technology and colleagues may have the answer. They have built a tiny production line in which a cell's membrane is temporarily opened up by squeezing it through a narrow channel at high speed.

The image shows a small part of the process. You can see four of 70 channels that can operate in parallel. The channels sit in a solution containing cells and whatever particle needs to be put inside them. About 50,000 cells are then forced through the channels each second.

As a cell squeezes through the channel, holes open up in its membrane and stay open for 30 to 60 seconds - long enough for the other particles in the solution to enter by diffusion.

Speed is important. "You've got to hit them hard enough," says Sharei. The challenge was in finding the right balance. "Too hard and it'll kill the cells, too soft and it doesn't work."

The slow-motion video above shows a cell passing through a channel in an early prototype of the device. In the latest version, the cells move so quickly that even high-speed cameras can't keep up. "You'd need to be able to capture about 200,000 frames a second," says Sharei.

This has posed a practical problem for the researchers: unable to see what happens, they must now use indirect methods such as computer simulations to observe how the cell membranes open.

In addition to its efficiency, the main advantage of this approach is that a carrier such as a virus is not needed, so there should be fewer side effects. "It's just the cell and what you want to put in it," says Sharei.

The technique should be particularly useful with immune cells, which are notoriously difficult to implant with drugs. For example, by running a cancer patient's blood through the device, you could implant a molecule that instructs their immune cells to target a specific part of a tumour, says Sharei.

Journal reference: PNAS, DOI: 10.1073/pnas.1218705110

Source: http://feeds.newscientist.com/c/749/f/10897/s/27dd8a3b/l/0L0Snewscientist0N0Cblogs0Cshortsharpscience0C20A130C0A10Ccell0Emembrane0Bhtml0Dcmpid0FRSS0QNSNS0Q20A120EGLOBAL0Qonline0Enews/story01.htm

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