Single threads of DNA can now be manipulated using miniaturised hooks and bobbins, thanks to Japanese scientists.

Taking their inspiration from sewing, Kyohei Terao from Kyoto University and colleagues designed these laser-directed microdevices to pick up and manoeuvre giant individual molecules of DNA.

 

Using miniaturised hooks and bobbins single DNA strands can be manoeuvred without breakage

 

Single molecule analysis of DNA is limited by the difficulty of stretching out and handling these long molecules - eukaryotic DNA can range from millimetres to centimetres. A giant DNA molecule is very fragile, explains Terao, so to catch it and manipulate it without breaking it is a challenge.  

Thinking of a strand of DNA as a piece of sewing thread, Terao developed microhooks to pick up the DNA, just like we would use our fingers to pick up thread. When thread is very long it becomes tiresome to manipulate it just with our fingers and instead we wind it around bobbins to make it compact. This is what inspired us to use microbobbins, says Terao.

Optical tweezers - where tightly focused laser beams trap and hold tiny objects - are used to catch and move these microdevices.   The z-shaped microhook is directed by the tweezers to pick up a single strand of DNA, and barbs in the openings of the hook prevent the caught DNA unhooking.   In the case of bobbins, two focused laser beams are used to revolve one bobbin around the other. The revolving motion winds the DNA molecule between the two bobbins.

This DNA manipulation technique should prove useful in applications such as fluorescence in situ hybridisation (FISH), says Terao. FISH is used to locate a gene on a DNA molecule using fluorescent gene markers, providing useful information for the diagnosis of genetic diseases and analysis of chromosome function. However, DNA has randomly-coiled conformations, which can hamper observations. But when a DNA molecule is manipulated and straightened by microhooks and bobbins, the gene location can be determined easily with high-spatial resolution, says Terao.

It is 'an excellent idea to fabricate unique microtools that enables us to manipulate a single giant DNA molecule', says Yoshinobu Baba, who researches biologically useful microdevices at Nagoya University, Japan.  The technology will also be useful for a number of other applications including DNA sequencing and molecular electronics, he adds.

Sarah Corcoran