Dopamine Sensors Capable of Tracking Chemical Release in the Brain

A carbon nanotube (CNT) is a cylindrical material made of carbon mesh, with diameters in the nanometer (nm) scale. These CNTs have intriguing electronic, magnetic and mechanical properties, while coming in a variety of structures of various lengths, thicknesses and number of layers.

CNTs are usually classified into either single-walled (SWCNTs), which resembles a straw with a single layer of nanotube making the wall, or multi-walled nanotubes (MWCNT), which are comprised of layers of cylindrical nanotubes enclosed in one another of increasing diameter. The number of tubes making up the MWCNT could vary from two to as many as 100.

The high strength, great flexibility, low weight, high conductivity of heat energy, and semiconducting properties of CNTs make it a great area of interest in the fields of nanotechnology, electronics, optics and material sciences1. Most recently, researchers at the Massachusetts Institute of Technology’s Department of Chemical Engineering have used SWCNTs to develop an extremely sensitive detector to track single cell secretion of dopamine, an important neurotransmitter (NT), in the brain.

NTs are brain chemicals used in chemical signaling between the nerve cells, or neurons, by establishing connections called ‘synapses’ to relay information back and forth from the brain to control various systems of the body involving heart, lungs, gastrointestinal tract, etc. There are NTs which stimulate the brain called excitatory NTs, of which include epinephrine, norepinephrine and histamine, as well as inhibitory neurotransmitters, such as serotonin and GABA, which are responsible for maintaining the balance of NTs in the body 2.

Dopamine is considered as both excitatory and inhibitory, which makes it an important NT in reward motivated behavior, learning and memory processes2,3. Some of the dopamine that is released at the synapse into the microenvironment will affect the nearby cells, causing a global effect, along with the local effect, through neuronal signaling.

Although tracking the release of dopamine could serve greatly in the field of neuroscience, tracking this dopamine diffusion has proven to be difficult until now.

In a recent study published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), researchers at MIT have developed sensitive dopamine sensors using SWCNTs to solve this problem. Michael Strano’s lab constructed a nanosensor by homogeneously coating SWCNTs on a silane glass, in which the sensor was then wrapped with polymers of specific single-stranded DNA nucleotide sequence for selectivity to catecholamines, like dopamine.

Neuroprogenitor pheochromocytoma cells (PC12) were then cultivated with collagen for easy adhesion on top of the sensor. When the dopamine is released by the PC12 cells upon stimulation by the potassium in the buffer, the phosphate group of the DNA backbone on the sensor interacts with the hydroxyl groups of dopamine, pulling the phosphate group closer to the surface of SWCNTs, and thus changing the local potential. Excitation of the SWCNTs was achieved by using a standard fluorescence microscope equipped with an nIR-camera and a laser of 560 nm, in which the subsequent nIR emission of ∼980 nm was achieved4.

The results of the dopamine response profile showed the heterogeneity along the cell contour, displaying that the anisotropy and the shape of the cells affect the distribution of the release sites of dopamine. Hotspots were related with anisotropic distribution of protrusions on the cell surface, indicating that dopamine release happens more frequently at these protrusions, but is not limited to the positive curvature4. This led researchers to postulate a possible mechanism in describing how these cells have the potential to shape a chemical signal.

Due to the interactions of the hydroxyl groups of the catecholamines with the phosphate groups of the DNA backbone, the nanodetector measured the total concentration of all catecholamines4. While this is a possible limitation of the device, PC12 cells are thought to mainly release dopamine, with a relatively negligible amount of ascorbic acid, validating that the levels of dopamine were primarily measured in this study.

References:

  1. "What Are Carbon Nanotubes?" Nanoscience. Web. http://www.nanoscience.com/applications/education/overview/cnt-technology-overview/.
  2. "What Are Neurotransmitters?" Neurogistics. Web. http://www.neurogistics.com/the-science/what-are-neurotransmitters.
  3. Trafton, Anne. "Sensor Traces Dopamine Released by Single Cells." MIT News. 06 Feb. 2017. Web. http://news.mit.edu/2017/sensor-traces-dopamine-released-single-cells-0206.
  4. Kruss, Sebastian, Daniel P. Salem, Lela Vukovia, Barbara Lima, Emma Vander Ende, Edward S. Boyden, and Michael S. Strano. "High-resolution Imaging of Cellular Dopamine Efflux Using a Fluorescent Nanosensor Array." Proceedings of the National Academy of Sciences (2017). Web.
  5. Image Credit: shutterstock.com/rvector

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