title: Presentation of large DNA molecules for analysis as nanoconfined dumbbells.
abstract: The analysis of very large DNA molecules intrinsically supports long-range, phased sequence information, but requires new approaches for their effective presentation as part of any genome analysis platform. Using a multi-pronged approach that marshaled molecular confinement, ionic environment, and DNA elastic properties-but tressed by molecular simulations-we have developed an efficient and scalable approach for presentation of large DNA molecules within nanoscale slits. Our approach relies on the formation of DNA dumbbells, where large segments of the molecules remain outside the nanoslits used to confine them. The low ionic environment, synergizing other features of our approach, enables DNA molecules to adopt a fully stretched conformation, comparable to the contour length, thereby facilitating analysis by optical microscopy. Accordingly, a molecular model is proposed to describe the conformation and dynamics of the DNA molecules within the nanoslits; a Langevin description of the polymer dynamics is adopted in which hydrodynamic effects are included through a Green's function formalism. Our simulations reveal that a delicate balance between electrostatic and hydrodynamic interactions is responsible for the observed molecular conformations. We demonstrate and further confirm that the "Odijk regime" does indeed start when the confinement dimensions size are of the same order of magnitude as the persistence length of the molecule. We also summarize current theories concerning dumbbell dynamics.
authors.affiliation: Laboratory for Molecular and Computational Genomics, Department of Chemistry, Laboratory of Genetics, and UW-Biotechnology Center, University of Wisconsin-Madison, Madison, WI 53706-1580.
authors.forename: Kristy L
authors.initials: KL
authors.lastname: Kounovsky-Shafer
authors.affiliation: Departamento de Materiales, Universidad Nacional de Colombia, Sede Medellín, Kra 80 # 65-223.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Hernández-Ortiz
authors.affiliation: Bloque M3-050, Medellín Colombia, Department of Chemistry, Sogang University, Seoul, Korea.
authors.forename: Kyubong
authors.initials: K
authors.lastname: Jo
authors.affiliation: Lorentz Institute for Theoretical Physics, University of Leiden, The Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: Odijk
authors.affiliation: Institute for Molecular Engineering, University of Chicago, Chicago, IL 60637.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: de Pablo
authors.affiliation: Laboratory for Molecular and Computational Genomics, Department of Chemistry, Laboratory of Genetics, and UW-Biotechnology Center, University of Wisconsin-Madison, Madison, WI 53706-1580.
authors.forename: David C
authors.initials: DC
authors.lastname: Schwartz