DNA nanomachine can predict pH of live cells
Yamuna Krishnan and her colleague, Souvik Mody at the National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore have designed a nanomachine by joining DNA pieces.
Yamuna explained the device as composed of three short DNA strands. When there are protons in the medium and it is acidic, there is a shape change in the DNA strands.
This shape is lost when there are no protons. It is like a pair of ice tongs, which has two confirmations, an open state and a closed state. The whole structure is only about 7 nanometres.
Fluorescent tags
The DNA has fluorescent tags attached to it, which glow green in the open state and the pH is neutral. In the closed state, say when pH is about 4, the shape is a closed state and the fluorescence is red. The pH is low when there are more protons.
The DNA will be in different states of being open and closed depending upon the concentration of protons. It will glow green in the absence of protons and red when there are many protons. The colour changes accordingly — green to lime green … dark orange to red. These experiments were on fruit fly cell lines but they could be done in mammalian cells, too.
How many of these assemblies would therefore be typically required to read the pH of a group of cells? “More experiments will be needed to ascertain that,” says Dr. Krishnan. “The important aspect of this machine is that it gives specific information about a specific part of the cell.”
Nutrients and viruses reach the cell membrane and move into the cell using a process called as endocytosis. Here, the DNA is stuck on a protein called Transferrin, which gets into a cell through endocytosis. Transferrin is specific to a region of the cell and hence delivers the DNA to this region.
Dr Krishnan opines that, “If we could correlate changes in acidity and therefore pH, in a cell to a disease; this machine could play a role in sensing the pH change.” Viruses enter cells through the endocytic pathway and modulate the acidity of the cell. This device could combat virus entry by indicating the presence of viruses in the cell.
When any nutrient or a foreign object enters a cell, it moves through the cell with a characteristic rate of change of pH. At every step it has an associated pH and if the pH does not reach the level that it should, then it could lead to a different disease.
pH may not be the reason why something happens but it could be a good molecular correlate of biochemical events. We can actually see what the chemical changes in the cell can lead to. Similarly, cancer cells have varying pH and acidity.
Dr. Krishnan also works on using DNA capsules for drug delivery. Apart from other applications, the DNA capsules could prevent dangerous drugs from leaking out until they reach their intended targets.
Drug capsule
About the drug capsule, she says, “The DNA shell could also allow attachment to a protein that could ferry the drug-loaded capsule to a target cell. So, someone on chemotherapy need not swallow a lot of drugs, as patients have to, today. They have to suffer a lot of side effects because the medicine is directed to the good and bad cells.
Here, the medicine is directed only to the bad cells by programmed containers.”
PAPIYA BHATTACHARYA
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