Surana S, Bhat JM, Koushika SP, Krishnan Y. An autonomous DNA nanomachine maps spatiotemporal pH changes in a multicellular living organism. Nat Commun. 2011 Jun 7; 2:340.

Monitoring pH changes in vivo using a DNA sensor

Many physiological phenomenon inside living organisms such as development of an embryo, secretion and cell-cell fusion are associated with changes in pH which are difficult to track.  For the first time, Yamuna Krishnan and colleagues at NCBS, Bangalore, have successfully tested a DNA based nanodevice inside a worm that can sense changes in pH inside cell organelles.

The nanomachine or the I-switch is made of two DNA duplexes connected by a flexible hinge. Each end of the duplex has special nucleotides which bind to each other when pH is acidic and remain apart when it is neutral. Additionally, two fluorophore molecules are attached one to each end of the duplex such that their interaction is directly proportional to the distance between them. Hence, change in pH is directly reflected in the efficiency of energy transfer between the two fluorophores which can be monitored outside the organism.

In the study, the nanodevice was injected in the nematode Caenorhabditis elegans, where it entered the specialized cells called coelomocytes and was trapped in membrane-bound vesicles called endosomes. Endosomes are known to undergo a series of maturation stages each of which is associated with a change in pH. Scientists were able to track each stage of endosome maturation by monitoring the energy transfer efficiency between two fluorophores of the nanomachine.

Initial studies with this device were performed in cellular media and were highly successful. However, the fact that the nanomachine works robustly even in a more complex living organism is a huge step forward in the development of small-molecule sensors to monitor biological processes.     

-- Jaya Bhatnagar