In a study published in Nature Communications, researchers in Japan describe a novel way to control the delivery of nitric oxide (NO) gas into cells.
Nitric oxide is an important gas in the body that has numerous functions. It notifies cells when it is time to divide, dilates blood vessels and transmits signals between nerve cells in the brain. Understanding how nitric oxide controls these processes may lead to the development of novel therapeutic strategies to combat cancer and neurodegenerative diseases.
Yet, despite all that is known, scientists have struggled to uncover where and how much nitric oxide is needed in order for the gas to exert a specific effect. "No existing technique has been able to capture what this gas is truly doing at the cellular level," said Stephane Diring, who led the study.
The team of researchers, from Kyoto University's Institute for Integrated Cell-Material Sciences (iCeMS), tackled this problem head-on by combining chemical and biological approaches. They first created crystals of metal organic frameworks (MOF) -- mesoscopic cage-like structures ranging in size from ten to hundreds of nanometers. The researchers fused these so called cages with a material that, upon stimulation with light, produced nitric oxide.
"By itself, the material has low reactivity but when combined with the MOF, gas production skyrocketed over 50 times," said Diring. "Essentially, we built a crystal that can deliver gas on demand."
The scientists next went on to test this approach by cementing these frameworks into a thin, porous polymer surface, which was covered by a layer of cells. An infrared beam, projected from below the polymer stimulated the crystals to make nitric oxide, which traveled through the pores and into the cells. Using a fluorescent indicator, they were able to visualize both the gas entering into cells and stimulating proteins on the cell surface that allowed a flood of ions inside.
Another way to think about the system is to imagine an underground sprinkler network that is used to water a lawn. Except in this case, instead of water and grass, nitric oxide is released to feed into cells.
"The precise location and the amount of nitric oxide delivered are tunable based on the intensity and wavelength of the light," said fellow researcher Shuhei Furukawa. "Best of all, because the type of light we use is infrared, cells are not harmed in the process and it is completely safe."
"This is just the first step in using MOFs as on demand delivery vehicles," said principal investigator Susumu Kitagawa. "The system we made now will help with discoveries about nitric oxide in physiological processes, but we can also design MOFs with different payloads to study various gases and their effects."