(3ee) Modeling and Simulation of Interphase DNA and the Programmable Self-Assembly of DNA-Coated Nanoparticles

Despite the discovery of the double helix structure of DNA in 1953, the spatial arrangement of the genome remains poorly understood on length scales above that of nucleosomes or a few tens of nanometers. Progress on the genome folding problem has been made in recent years due to experimental methods with the HiC method being the most notable. While it has been known for decades that chromosomes remain in distinct territories during the interphase of the cell cycle, a key finding from these latests experiments is that on the scale of 0.7-10 million base pairs the chromatin fiber within a chromosome is organized in an unentangled, hierarchal structure called a fractal globule. A melt of unknotted nonconcatenated ring polymers can serve as a simple model for such a system largely because rings are unentangled and they lack free ends so reptation is suppressed. We have conducted molecular dynamics simulations using a bead-spring model to study the statics, dynamics and rheology of ring polymer melts. For comparison linear chains are also studied. Topological interactions cause the rings to be partially collapsed and partially segregated. Additionally, the contact probability of monomers within a single ring is found to follow a power law consistent with a fractal globule, as is also the case for human chromosomes. Proposed research involves investigating the model further by studying the diffusive motion of a particle in a ring polymer melt and by examining the mechanism of stress relaxation of the rings due to a rapid change in density.

Today DNA can be synthesized in the laboratory with any desired sequence. This capability provides a route to the programmable self-assembly of nanoparticles. Nanoparticles have novel optical, electronic, magnetic and chemical properties due to their small size. Envisaged applications such as nanoplasmonics require the nanoparticles to be precisely arranged into structures with a specific overall shape. Nanoparticles coated with ssDNA can form effective bonds with other particles through the hybridization of complementary strands. In principle, an arbitrary nanostructure can be encoded by using a large number strands. Using a coarse-grained model we have conducted computer simulations to study the self-assembly of pre-programmed finite clusters from an initially homogeneous nanoparticle solution. We find that the constituent nanoparticles can be designed such that the clusters are produced in near perfect yield and free from errors. In addition, by controlling the kinetic pathway the clusters form rapidly.

While the experimentalist is able to vary the particle size and shape it is still a challenge to controllably decorate nanoparticles with multiple strand types. However, even with only a small number of strand types a wide variety of structures have been produced and the resulting structures are often not easily understood. Proposed research involves developing models for these systems and conducting simulations to explain the dynamics of self-assembly and the phase behavior.

Research carried out in part at the Center for Functional Nanomaterials, Brookhaven National Laboratory, which is supported by the U.S. Department of Energy, Office of Basic Energy Sciences, under Contract No. DE-AC02-98CH10886.