If you could chop up a meter-long stick into a billion little pieces, each would be a nanometer (nm) long. Materials made of particles with diameters in the nanoscale range are being used in targeted pharmaceuticals, sensors, devices that capture and store energy and a variety of emerging applications.
Scientists have now used particles less than 500nm in diameter to modulate electrical activity in neurons of the brain and muscle cells of the heart. This non-genetic technology that modulates the activity of excitable cells through light offers a minimally invasive method for controlling cellular activity and may serve as a valuable tool in nano-neuroscience and nano-engineering.
The findings are reported in the article “Reversible Photothermal Modulation of Electrical Activity of Excitable Cells using Polydopamine Nanoparticles” in the journal Advanced Materials. Financial support for the study came from the Air Force Office of Scientific Research and the National Institutes of Health (NIH).
Researchers led by Srikanth Singamaneni, PhD, a materials scientist, and Barani Raman, PhD, a biomedical engineer, at the McKelvey School of Engineering at Washington University in St. Louis collaborated to develop this noninvasive technology that inhibits electrical activity using polydopamine (PDA) nanoparticles and near-infrared light. Negatively charged PDA nanoparticles selectively bind to the surface of cells such as neurons or muscle cells and absorb near-infrared light generating heat. This heat is then transferred to the cells inhibiting their electrical activity.
“We showed we can inhibit the activity of these neurons and stop their firing, not just on and off, but in a graded manner,” says Singamaneni, the Lilyan & E. Lisle Hughes Professor in the Department of Mechanical Engineering & Materials Science. “By controlling the light intensity, we can control the electrical activity of the neurons. Once we stopped the light, we can completely bring them back again without any damage.”
A bonus of using PDA nanoparticles to modulate cellular activity is that they are highly biocompatible and biodegradable making them a convenient tool for use in experiments done in a dish or in an organism.
“When you pour cream into hot coffee, it dissolves and becomes creamed coffee through the process of diffusion,” says Singamaneni. “It is similar to the process that controls which ions flow in and out of the neurons. Diffusion depends on temperature, so if you have a good handle on the heat, you control the rate of diffusion close to the neurons. This would in turn impact the electrical activity of the cell. This study demonstrates the concept that the photothermal effect, converting light into heat, near the vicinity of nanoparticle-tagged neurons can be used as a way to control specific neurons remotely.”
Better still than using the PDA nanoparticles in a colloidal solution, is using them in a compact 3D collagen foam. This offers the added advantage of spatial control over photothermal stimulation using near infrared light, and thereby better photothermal performance.
Collagen foam is widely used in biomedical applications such as wound dressing and tissue culture scaffolds. It is highly porous and also biocompatibility. It scatters light and is therefore white and does not possess photothermal activity. The foam forms a thick package of nanoparticles on the surface of cells allowing quicker photothermal modulation than individual nanoparticles.
“With so many of them packed in a small volume, the foam is quicker in transducing light to heat and gives more efficient control to only the neurons we want,” says Singamaneni. “You don’t have to use high-intensity power to generate the same effect.”
Collaborating scientist, Jon Silva, PhD, associate professor of biomedical engineering, and the team, also applied the PDA nanoparticles to heart muscle cells and successfully excited the cells using the near-infrared light, showing that the process can increase or decrease the excitability in cells depending on their specific characteristics.
“The excitability of a cell or tissue, whether it be cardiomyocytes or muscle cells, depends to a certain extent on diffusion,” says Raman. “While cardiomyocytes have a different set of rules, the principle that controls the sensitivity to temperature can be expected to be similar.”
The next step for the team is to see how different types of neurons respond to the photothermal process. To accomplish this, they are looking into selectively binding nanoparticles to target specific neurons.