Soccer-ball-shaped
“buckyballs” are the most famous players
on the nanoscale field, presenting
tantalizing prospects of revolutionizing
medicine and the computer industry.
Since their discovery in 1985, engineers
and scientists have been exploring the
properties of these molecules for a wide
range of applications and innovations.
But could these
microscopic spheres represent a
potential environmental hazard?
A new study
published in December 2005 in
Biophysical Journal raises a red flag
regarding the safety of buckyballs when
dissolved in water. It reports the
results of a detailed computer
simulation that finds buckyballs bind to
the spirals in DNA molecules in an
aqueous environment, causing the DNA to
deform, potentially interfering with its
biological functions and possibly
causing long-term negative side effects
in people and other living organisms.
The research,
conducted at Vanderbilt by chemical
engineers Peter T. Cummings and Alberto
Striolo (now a faculty member at the
University of Oklahoma), along with Oak
Ridge National Laboratory scientist
Xiongce Zhao, employed molecular
dynamics simulations to investigate the
question of whether buckyballs would
bind to DNA and, if so, might inflict
any lasting damage.
“Safe is a
difficult word to define, since few
substances that can be ingested into the
human body are completely safe,” points
out Cummings, who is the John R. Hall
Professor of Chemical Engineering and
director of the Nanomaterials Theory
Institute at Oak Ridge National
Laboratory.
“Even common
table salt, if eaten in sufficient
quantity, is lethal. What we are doing
is looking at the mechanisms of
interaction between buckyballs and DNA;
we don’t know yet what actually happens
in the body,” he says.
Surprising
findings
Despite the
caveat, Cummings suggests that his
research reveals a potentially serious
problem: “Buckyballs have a potentially
adverse effect on the structure,
stability and biological functions of
DNA molecules.”
The findings
came as something of a surprise, despite
earlier studies that have shown
buckyballs to be toxic to cells unless
coated and to be able to find their way
into the brains of fish. Before these
cautionary discoveries, researchers
thought that the combination of
buckyballs’ dislike of water and their
affinity for each other would cause them
to clump together and sink to the bottom
of a pool, lake, stream or other aqueous
environment. As a result, researchers
thought they should not cause a
significant environmental problem.
Cummings’ team
found that, depending on the form the
DNA takes, the 60-carbon-atom (C60)
buckyball molecule can lodge in the end
of a DNA molecule and break apart
important hydrogen bonds within the
double helix. They can also stick to the
minor grooves on the outside of DNA,
causing the DNA molecule to bend
significantly to one side. Damage to the
DNA molecule is even more pronounced
when the molecule is split into two
helices, as it does when cells are
dividing or when the genes are being
accessed to produce proteins needed by
the cell.
“The binding
energy between DNA and buckyballs is
quite strong,” Cummings says. “We found
that the energies were comparable to the
binding energies of a drug to receptors
in cells.”
It turns out
that buckyballs have a stronger affinity
for DNA than they do for themselves.
“This research shows that if buckyballs
can get into the nucleus, they can bind
to DNA,” Cummings says. “If the DNA is
damaged, it can be inhibited from
self-repairing.”
Computer
simulations
The computer
simulations showed that buckyballs make
first contact with the DNA molecule
after one to two nanoseconds. Once the
C60 molecules bind with the DNA, they
remained stable for the duration of the
simulation.
Researchers
tested the most common forms of DNA, the
“A” and “B” forms. The “B” form is the
most common form. In a stronger saline
solution, or when alcohol is added, the
DNA structure can change to the “A”
form. A third, rarer form, “Z,” occurs
in high concentrations of alcohol or
salt and was not tested.
The researchers
found that buckyballs docked on the
minor groove of “A” DNA, bending the
molecule and deforming the stacking
angles of the base pairs in contact with
it. The simulations also showed that
buckyballs can penetrate the free end of
“A” form DNA and permanently break the
hydrogen bonds between the end base pair
of nucleotides.
As expected, the
buckyballs bound most strongly to single
helix DNA, causing the most deformation
and damage. While buckyballs did bind to
“B” form double-strand DNA, the binding
did not affect the overall shape of the
DNA molecule.
More research
needed
What the
researchers don’t know is whether these
worrisome binding events will take place
in the body. “Earlier studies have shown
both that buckyballs can migrate into
bodily tissues and can penetrate cell
membranes,” Cummings says. “We don’t
know whether they can penetrate a cell
nucleus and reach the DNA stored there.
What this study shows is that if the
buckyballs can get into the nucleus they
could cause real problems. What are
needed now are experimental and
theoretical studies to demonstrate
whether they can actually get there.
Because the toxicity of nanomaterials
like buckyballs is not well known at
this point, they are regarded in the
laboratory as potentially very
hazardous, and treated accordingly.”
Source:Vanderbilt University
Published on 14th
December 2005
