What DNA does when it stretches

What DNA does when it stretches

The molecule of life has some interesting elastic properties

By Daniel Strain

Web edition
: Wednesday, January 26th, 2011

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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, 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

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