Using nanoparticles as photothermal nanotransducers, scientists at Washington University in St. Louis demonstrated reversible modulation of electrical activity in excitable nerve and heart muscle cells. The biocompatible, minimally invasive approach to controlling electrical activity in cells could be a valuable tool for neuroscientists and neuroengineers. Teams led by Srikanth Singamaneni, a materials scientist, and Barani Raman, a biomedical engineer, collaborated to develop a method to suppress the spike rate of neurons and the beating rate of cardiomyocytes using polydopamine (PDA) nanoparticles irradiated with near-infrared light. When the negatively charged PDA nanoparticles absorb near-infrared light, they generate heat. The nanoparticles, which selectively bind to neurons, transfer heat to the neurons, inhibiting the neurons’ electrical activity. The researchers were able to maintain precise control over the neurons’ electrical movements, and even reverse activity by varying the excitation power and irradiation time. “By controlling the light intensity, we can control the electrical activity of the neurons. Once we stop the light, we can completely bring them back again without any damage,” Singamaneni said. “We showed we can inhibit the activity of these neurons and stop their firing, not just on and off, but in a graded manner.” Schematic of polydopamine nanoparticle (PDA NP)-mediated photothermal stimulation of neurons. PDA nanoparticles localized on the neuron membrane (blue figure, left) modulate the neural activity through photothermal conversion of NIR light (red image). On right: SEM image of neurons on electrode (inset: higher-magnification SEM). Courtesy of Washington University in St. Louis/Srikanth Singamaneni. Raman said that the flow of ions in and out of the neurons depends on the temperature of the nanoparticles: “Diffusion depends on temperature, so if you have a good handle on the heat, you control the rate of diffusion close to the neurons,” he said. “This in turn would impact the electrical activity of the cell.” When the researchers applied the irradiated PDA nanoparticles to cardiomyocytes, the cardiomyocyte cells were excited, demonstrating that the photothermal process performed by the nanoparticles could either increase or decrease excitability, depending on the type of cell. “While cardiomyocytes have a different set of rules, the principle that controls the sensitivity to temperature can be expected to be similar,” Raman said. Under optimal conditions, the researchers were able to show reversible suppression of neural activity of about 100% and a twofold reversible enhancement in the beating rate of cardiomyocytes. To make it easier for the nanoparticles to interface with the cells, the researchers designed a collagen/PDA nanoparticle foam — a dense population of nanoparticles in tight packaging — that can be used to speed and support the process of photothermal stimulation. “With so many of them packed in a small volume, the foam is quicker in transducing light to heat and gives [us] more efficient control [over] only the neurons we want,” Raman said. “You don’t have to use high-intensity power to generate the same effect.” In addition to their broad light absorption and excellent photothermal activity, PDA nanoparticles are biocompatible and biodegradable, making them good candidates for both in vitro and in vivo applications. The researchers believe that their approach to controlling electrical activity in excitable cells could be translated to other cell types. They are currently investigating how different types of neurons respond to the photothermal stimulation process, and they plan to target specific neurons by selectively binding the nanoparticles to them. The research was published in Advanced Materials (www.doi.org/10.1002/adma.202008809).