DNA ― springy, stretchy and coiled ― is the cell’s Slinky. And just like a Slinky, a DNA double helix can be stretched too far. The mechanics behind this process, called “overstretching,” may be less cut-and-dried than scientists previously thought, a new study suggests.
Contrary to one prevailing theory, DNA molecules don’t have to have loose-hanging single strands — called free ends— to overstretch, say researchers at the National Institute of Standards and Technology in Boulder, Colo. With or without free ends, the team reports in a paper to appear in the
Journal of the American Chemical Society
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, DNA double helices spring to almost twice their length at the same elastic stretching point.
Like a Slinky, DNA plays nice under tiny forces, stretching as molecular theory predicts. But when scientists pull on these molecules hard enough using devices called optical traps, DNA seems to get extra elastic. At 65 piconewtons of force — each piconewton equals one trillionth of a newton, itself equal to roughly the gravitational force on a typical apple — DNA elongates by 70 percent. “Within a few piconewtons, the molecule goes from normal DNA to overstretched DNA,” says biophysicist and study coauthor Thomas Perkins.
Many biophysicists eyed free ends as the possible culprits behind this sudden spring. Until recently, when researchers pinned down DNA prior to games of microscopic tug-of-war, they often left one of the two strands unsecured at one end. This allowed the whole double helix to twist and turn normally when stretched. But it also left one strand wild. Many researchers theorized that with enough stretch, this loose strand could peel away from the second like a piece of string cheese, making the DNA much more elastic.
In 2009, an international team of researchers took snapshots of overstretched DNA in the presence of fluorescent proteins that bind only to relaxed, single-stranded DNA. And, indeed, at 65 piconewtons, the DNA started to glow, highlighting the presence of free-wheeling single-stranded DNA. For many biophysicists, the debate seemed settled.
Perkins and his team, however, designed a stretching experiment that both eliminated free ends and let the DNA twirl. They looped both strands together at the tips using a small patch of additional DNA, then pinned down the molecule by that loop. With or without free ends, DNA still overstretched at 65 piconewtons
“This is a really smart innovation,” says Erwin Peterman, a biophysicist at VU University Amsterdam and one of the authors of the 2009 study. “We should have thought about it ourselves.” Smart as it is, this study doesn’t make the picture of DNA stretching any simpler, says Mark C. Williams, a biophysicist at Northeastern University in Boston who was not involved in either study. “You can have peeling from the ends,” he says, “but if you can’t peel from the ends, it still does essentially the same thing.”
The double helices could still be slipping apart, he says, just from the middle out — like an expanding bubble. But, as some researchers have suggested, at high forces DNA could also form a modified structure called S-DNA. S-DNA, a straightened, ladder-like DNA molecule, may have more give between its rungs than the traditional double helix.
Since DNA consistently overstretches at 65 piconewtons during experiments, Perkins suggests that these molecules could be used to define wee forces like the piconewton. In other words, machines could tick off 65 piconewtons the instant DNA overstretches. But without knowing exactly how the molecule gets so limber, that sort of calibration is still an uncertain venture, he says.
One thing, however, is certain. Unlike the single-helixed Slinky, science has yet to find a way for DNA to walk down stairs.