AUSTIN, Texas By using the molecular-recognition capabilities of living cells, scientists have made selective electrical contacts to neurons. The cadmium sulfide contacts act as photodetectors, allowing researchers to communicate with the cells using precise wavelengths of light.
By selectively coding peptides that coated quantum dots, University of Texas scientists precisely controlled the spacing of hundreds of quantum dots on the surface of the living neurons.
"We are taking small particles of semiconductor materials, our quantum dots," said Christine Schmidt, an assistant professor of biomedical engineering. "These are cadmium sulfide-based materials. We can take peptide molecules that have very specific protein sequences and put them into the actual semiconductor material, which then very specifically binds to particular locations on cell surfaces."
Schmidt performed the work with Brian Korgel, an assistant professor of chemical engineering, and doctoral candidates Jessica Winter and Timothy Liu.
Scientists had already attached a variety of objects to cells using biorecognition, such as fluorescent dyes, enzymes and radioactive labels, but Schmidt said her group is the world's first to intentionally interface with neurons electrically. Others have implanted relatively large electrode grids into patients and encouraged neuron growth over the grid arrays. But there was still about a 1-micron gap between the neurons and the electrodes. Schmidt's method slims that down to 3 nanometers.
"What's unique about it is that we can do this on a very very small-length scale that we can really pull the semiconductor material directly to the cell surface using these very short [roughly 3-nm] peptide sequences," she said. "We can distribute them to different parts of the cell depending on what we want to trigger."
Cadmium sulfide has been commonly used in inorganic experiments in which tiny nanometer-scale "quantum dots" are deposited on a substrate. The dots are able to corral a few electrons and, researchers hope, build extremely dense logic circuits using the technique.
In this new biological application, attaching quantum dots directly to cells eliminates the need for external electrodes. The procedure is entirely non-invasive, similar to the use of fluorescent dyes to mark cells. And since molecular recognition is used, it is a "smart" technology that can pick precisely which capability will be controlled on each neuron to which a quantum dot is attached. Taken to the logical extreme, biologists could remotely control any neural function by activating select neurons.
"Presumably, in the future we will be able to turn on an ion channel or turn off something else," said Schmidt. "We could have highly regulated activity in the neuron. . . . One idea is to put a quantum dot right next to a protein channel one that opens and closes allowing ions to go in and out, and basically control the ion exchange, which in turn controls action potentials [neuron 'firing']. These are the electrical signals with which the neuron interacts with the brain."
Using mercury vapor lights, the researchers induced photoluminescence of visible light from quantum dots directly attached to neurons. Filters fine-tuned the wavelength to activate the quantum dots. Cells were repeatedly activated for 10 days. At the end of that time, Schmidt said, they showed no significant health difference from the control cells to which no quantum dots were attached.
Researchers attached quantum dots to living neurons using both antibody and peptide molecular recognition, but the peptide recognition enabled the researchers to demonstrate nanometer-scale control over targeting, as well as separation distances between quantum dots and the cell.
"One approach is to synthesize the peptide into one of the layers of the quantum dot, and in another approach we are actually using a peptide that through biorecognition attaches itself to the semiconductor automatically," said Schmidt. "The other side of the peptide then recognizes very particular receptors on the cell's surface, and in that way we get highly specific interactions between the quantum dot and the neuron."
The quantum dots were synthesized from a solution of cadmium and sulfur atoms using the precipitation method. The quantum dots that resulted were on the order of 45 angstroms in diameter small enough to enable them to exhibit very promising optical and electrical properties while interfaced with the neurons.
"We specifically pinned them down to a cell and used optical techniques to activate the quantum dots all over the cell," said Schmidt. "We are also looking into making composites of living cells and quantum dots tissue globs essentially where we can then activate the dots with light to trigger, for instance, a drug delivery application."
An audio recording of reporter R. Colin Johnson's full interview with Christine Schmidt can be found online at AmpCast.com/RColinJohnson.