the Interaction Between Nanoscale Building Blocks and Biologically
X. Zhao (CNMS Postdoc), A. Striolo (U of Oklahoma, now CNMS User), and
P. T. Cummings (CNMS Staff)
Scientists at Oak
Ridge National Laboratory’s new Center for Nanophase
Materials Sciences (CNMS) are leading the way in developing detailed
molecular-level understanding of how nanomaterials may interact with
biologically important molecules. A provocative experimental study, published
in 2004, suggested that juvenile largemouth bass, when exposed to plain
fullerenes (C60 “buckyballs”) suspended in water, exhibited
oxidative stress, indicating that the fullerenes can be absorbed into
living tissue. This led CNMS researchers to investigate the potential
impact of buckyballs if they managed to penetrate not only into cells
but into the cell nucleus to interact with DNA. With the molecular simulation
tools and computing hardware available today, it is possible to ask this
question computationally before carrying out experiments. The surprising
prediction  is that buckyballs bind very strongly to DNA, with binding
energies of between -27 and -42 kcal/mol (i.e., about 50 to 80 times
larger than typical kinetic energies at room temperature). The binding
is so strong that it deforms the DNA; it appears to impact the ability
of DNA to self-repair; and it is likely to interfere with replication,
resulting in significant health risks, if we presume that there is a
way for buckyballs to reach the cell nucleus. However, these findings
need to be confirmed experimentally.
Neutron scattering experiments now are planned in collaboration with
researchers in the Spallation Neutron Source at ORNL to verify the predicted
deformation of DNA. Additionally, the likelihood of buckyballs penetrating
cell membranes and the cell nucleus must be determined by a combination
of experimental and computational techniques.
Using the computational expertise and tools at the CNMS and ORNL for
early evaluation of potential nanotoxicological risk is a prudent and
economical way to identify and understand potential risks before nanomaterials
are used (or are even available) on a large scale.
Long (up to 20 ns in length) molecular dynamics simulations of DNA strands
in aqueous solution with C60 fullerenes exhibit strong binding to both
the end (above right) and minor groove (below right) of double strand
DNA. Similar results are obtained for single strand DNA.
Publication: “C60 Binds
to and Deforms Nucleotides,” Biophysical
Journal 89, 3856 (2005).