Space balls. In conventional fluorescence methods, interactions between organic dye tags (red and green) are used to measure distance.

Watching DNA Bind

ANAHEIM, CALIFORNIA--For researchers looking to monitor the nanoscale movement of biomolecules, good techniques are hard to come by. Current fluorescent methods work only over very short distances, and the fluorescence itself is short-lived. Now a group has come up with a novel molecular ruler that solves both problems at once.

At the Nano Science and Technology Institute's Nanotech 2005 meeting here last week, University of California (UC), Berkeley chemist Paul Alivisatos reported a way to use pairs of gold nanoparticles to measure distances out to 70 nanometers and keep track of their targets indefinitely. Gold nanoparticles have been used for sensing since 1997, when a team at Northwestern University developed a scheme for detecting specific snippets of DNA with a simple color-change test. As particular DNA strands bound each other, they pulled attached gold particles together tightly enough to change the way their electrons moved, altering the wavelengths of light the particles scattered and changing their color (Science, 22 August 1997, p. 1036). Although the experiment used hordes of nanoparticles to create a color change visible to the naked eye, other studies suggested that even two particles should produce a shift visible through a microscope.

Alivisatos and colleagues decided to see for themselves. First, using a pair of proteins as molecular glue, they bound 40-nanometer gold nanoparticles to a glass slide. When they shined white light on the slide, far-apart particles scattered green light most strongly, with a wavelength of about 540 nanometers, while closer particles shifted to the red end of the spectrum by about 20 nanometers.

With their new molecular ruler in hand, the researchers set out to track the binding and unbinding of DNA. They started with a solution of pairs of gold nanoparticles tethered by snippets of single-stranded DNA. Under white light, the particles scattered light at about 550 nanometers. The researchers then added DNA strands that were complementary to the tethers. The newly introduced DNA strands bound to the tethers, stiffening them enough to push the nanoparticles apart by about 2 nanometers. As that happened, the wavelength of light scattered by the nanoparticles shifted toward the blue end of the spectrum by a few nanometers.

"It's really cool," says Thomas Kipps, a cancer cell biologist at UC San Diego. By extending the length of the ruler, he says, scientists may be able to track events from the binding of DNA strands to one another to the ability of proteins called transcription factors to bind with and initiate genetic transcription.

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