Simulated Buckyballs Bind to DNA

Still unknown:  Whether they can get inside cells

Recent research illustrates a nightmare scenario for nanotechnology: simulated particles called buckyballs eagerly glomming onto nearby DNA. The study, published in Biophysical Journal in December 2005, has been widely read as a warning against the use of such materials for drug delivery, or any other purpose that could release them into the environment.
“If [buckyballs] can get into the cell, and into the nucleus, then they look like they have a significant impact on the DNA,” says co-author Peter Cummings, PhD, professor of chemical engineering at Vanderbilt University in Nashville, Tennessee, and director of the Nanomaterials Theory Institute at Oak Ridge National Laboratory.


Simulated buckyballs start near a DNA strand.But because buckyballs’ ability to enter the cell nucleus is by no means certain, Cummings emphasizes it’s too early to suggest that buckyballs are unsafe. “This [simulation] is showing a possibility of what buckyballs could do,” Cummings says. “Now it’s worth investigating to find out if they can actually get into the cell and if they can do this kind of damage.”
Buckyballs—also known as buckminsterfullerenes—are hollow, soccer-
ball-shaped carbon molecules that, researchers believe, have the potential to transmit electricity or deliver drugs to targets inside the human body. Safety concerns were raised by a 2004 experiment that detected buckyballs accumulating in the brain tissue of fish. This finding prompted Cummings’ group to investigate buckyballs’ behavior inside cells.


Cummings and collaborators at Oak Ridge National Laboratory ran computer simulations of buckyballs placed in saline solution near a short strand of DNA. Within two nanoseconds, the buckyballs either stuck to the free end of the DNA or lodged into the minor groove between the two strands. Single-stranded DNA tended to wrap around the buckyballs, dramatically changing the DNA’s shape. On confronting a damaged piece of DNA, the buckyball wedged itself into the gap created by the tear.


Buckyballs quickly bind to hydrophobic sections of the genetic material (above). The twisted DNA-buckyball compound remains stable for the rest of the simulation. Courtesy of Xiongce Zhao, Oak Ridge National LaboratoryThese scenarios suggest that nanoscale materials such as buckyballs could interfere with DNA replication, transcription and repair. Such disruptions might cause long-term damage, including heritable mutations and cancer.


Scientists had predicted buckyballs would be harmless because they are hydrophobic, or water-hating. The nanoparticles were expected to bind to one another and “clump out” of solution. But it appears that inside a cell’s nucleus, buckyballs tend to latch onto hydrophobic sections of DNA molecules, rather than onto one another.


According to the model calculations, buckyballs form a strong bond with DNA (in the range -27 to -42 kcal/mol). This is comparable to the strength of a drug attaching to a receptor and four times the binding energy of one buckyball to another buckyball.


Cummings and other scientists caution, however, that these results must be verified in experiments before sounding the alarm. “This paper adds little to the debate over what might happen in the physiological milieu,” comments Martin Chaplin, PhD, an expert in water clustering at London South Bank University in the United Kingdom. The initial distance may be small enough that a dehydrating transition drew the buckyballs to the DNA, Chaplin says. He also questions representing a buckyball in solution exhibiting no electric charges. To address these concerns, Cummings is using x-ray diffraction to study actual buckyballs and DNA. He plans to run another simulation incorporating the same fluid that he uses in the experiment.


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