title: Modeling the relaxation of internal DNA segments during genome mapping in nanochannels.
abstract: 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 one-dimensional, 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.
authors: Department of Chemical Engineering and Materials Science, University of Minnesota-Twin Cities , 421 Washington Ave. SE, Minneapolis, Minnesota 55455, USA.
authors: Aashish
authors: 0000-0001-7580-8694
authors: A
authors: Jain
authors: Department of Chemical Engineering and Materials Science, University of Minnesota-Twin Cities , 421 Washington Ave. SE, Minneapolis, Minnesota 55455, USA.
authors: Julian
authors: 0000-0002-0293-702X
authors: J
authors: Sheats
authors: BioNano Genomics , 9640 Towne Centre Drive, Suite 100, San Diego, California 92121, USA.
authors: Jeffrey G
authors: JG
authors: Reifenberger
authors: BioNano Genomics , 9640 Towne Centre Drive, Suite 100, San Diego, California 92121, USA.
authors: Han
authors: H
authors: Cao
authors: Department of Chemical Engineering and Materials Science, University of Minnesota-Twin Cities , 421 Washington Ave. SE, Minneapolis, Minnesota 55455, USA.
authors: Kevin D
authors: KD
authors: Dorfman