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We have developed a multi-scale model describing the dynamics of internal segments of DNA in nanochannels used for genome mapping. In addition to the channel geometry, the model takes as its inputs the DNA properties in free solution (persistence length, effective width, molecular weight, and segmental hydrodynamic radius) and buffer properties (temperature and viscosity). Using pruned-enriched Rosenbluth simulations of a discrete wormlike chain model with circa 10 base pair resolution and a numerical solution for the hydrodynamic interactions in confinement, we convert these experimentally available inputs into the necessary parameters for a onedimensional, Rouse-like model of the confined chain. The resulting coarse-grained model resolves the DNA at a length scale of approximately 6 kilobase pairs in the absence of any global hairpin folds, and is readily studied using a normal-mode analysis or Brownian dynamics simulations. The Rouse-like model successfully reproduces both the trends and order of magnitude of the relaxation time of the distance between labeled segments of DNA obtained in experiments. The model also provides insights that are not readily accessible from experiments, such as the role of the molecular weight of the DNA and location of the labeled segments that impact the statistical models used to construct genome maps from data acquired in nanochannels. The multi-scale approach used here, while focused towards a technologically relevant scenario, is readily adapted to other channel sizes and polymers.
Bibliographical noteFunding Information:
This work was supported by the National Institutes of Health (Grant No. R01-HG006851). We thank Seunghwan Shin for the measurement of the buffer viscosity. Part of this work was carried out in the College of Science and Engineering Polymer Characterization Facility, University of Minnesota, which has received capital equipment funding from the NSF through the UMN MRSEC program under Award No. DMR-1420013. Computational resources were provided in part by the Minnesota Supercomputing Institute at the University ofMinnesota. Jeffrey G. Reifenberger and Han Cao are employees of BioNano Genomics, which is commercializing nanochannel genome mapping.
How much support was provided by MRSEC?
Reporting period for MRSEC
- Period 3
PubMed: MeSH publication types
- Journal Article