Researchers devise nano-scale method for investigating living systems

By observing how tiny specks of crystal move through the layers of a biological membrane, a team of electrical and computer engineers and biologists has devised a new method for investigating living systems on the molecular level.

The discovery could lead to an entirely new level of manipulation, imaging and understanding of the inner workings of cells, according to the UW–Madison team led by electrical and computer engineers Dan van der Weide and Robert Blick. The work was recently published in the journal Applied Physics Letters.

The specks are known as quantum dots or inorganic semiconductor nanocrystals. Measuring in millionths of a millimeter, these dots are so small that the addition or removal of electrons changes the properties of the dot. The team, which also includes researchers Sujatha Ramachandran and George Kumar, found that by applying voltages to a solution of quantum dots and membranes similar to those of living cells, the dots would be pressed into the membranes. The dots formed rings, which in turn acted as portals in the membranes. These artificial portals or pores could enable a method of investigating living systems by means of semiconductor technology that until now could be theorized but not directly observed.

“To get a feeling of why this is important, you have to understand that each of our cell membranes has specific pores in them that regulate the flow of ions in and out,” says Blick. “Through these ions, your cells will build up electric potential and communicate with other cells. This is how signal transduction is performed in your body, but it is also how chemicals react with your body. When, for example, caffeine enters a cell it stimulates the opening and closing of these ion channels. What we’ve found is that these quantum dots can form artificial pores that enhance the flow of ions and which we can control from the outside via voltage.”

Quantum dots can be encoded with different colors, making them useful as fluorescent labels for staining cells. Their resistance to photobleaching and physical size of less than 10 nanometers are making them increasingly popular in biomedical applications ranging from intracellular tagging of molecules to applications such as tracking devices for neuronal receptors and as interfaces between nerve cells. Researchers have labeled the dots with isotopes, injected them into mice and then tracked them with tomography.

The Wisconsin engineering team set out to use optical tagging or labeling of membrane pores in order to visualize their function and simultaneously measure their current/voltage relationship.

“What we found was that quantum dots formed their own pores, which in the long run could mean that we could combine optical activity and readout with direct-current recording of cellular activity,” says Blick.

Because these artificial pores elicit bursts of current in the artificial membranes, the team believes quantum dots could perform similarly in other excitable cells such as neurons and muscles, and looks forward to understanding how the dots behave in vivo in excitable cells. The researchers will look next into properties that cause the artificial pores to open and close.