Dynamics of folding of a DNA segment inside a nano-channel
Prof. Aniket Bhattacharya (Department of Physics, University of Central Florida, USA)

<p>DNA is one of the most important biomolecules in living organism, forms a helix from two intertwined strands with complementary base pairs. Biological functions of a DNA depend on its mechanical properties, which in turn depend on its sequence specificity. Under physiological condition a double stranded DNA (dsDNA) is described as a semi-flexible biopolymer with persistence length of 50 nm, while a single-stranded DNA (ssDNA) is quite flexible. Recently straightening a dsDNA inside a nanochannel is being explored as an alternate method to determine DNA sequences at a single molecule level without replication. First, I will present coarse grained (CG) models for fast computations of DNA conformations and dynamics. I will use scaling arguments validated by Brownian dynamics (BD) simulation results performed on the CG models to demonstrate how the equilibrium DNA conformations change inside a nanochannel, as one varies the persistence length (stiffness) and the channel width [1, 2]. I will then show the transients and the steady states of an initially straightened DNA inside a nanochannel squeezed by a Nano- dozer assay. I will compare the time dependent density profiles from the BD simulation with those obtained from a Nonlinear Partial Differential Equation (NPDE) approach recently introduced by Khorshid et al., and demonstrate how this combined approach can be effectively used to study nonequilibrium dynamics of very long dsDNA segments inside a nanochannel [3]. For stiff chains in nanopores, we further show that chain compression proceeds through a unique folding kinetics driven by repeated double fold nucleation events and growth of nested folds. We show that the folding kinetics can be understood by coupling a theory for deterministic contour spooling across the folds with a dynamically varying energy landscape for fold nucleation. These findings are critical for understanding compression of nanochannel confined DNA in the sub-persistence length (Odijk) regime [4].<p>

1. Aiqun Huang and Aniket Bhattacharya, DNA confined in a two-dimensional strip geometry, Euro Phys. Lett. 106, 18004 (2014).

2. Aiqun Huang, H.-P Hsu, Aniket Bhattacharya, and Kurt Binder, Semiflexible macromolecules in quasi-one-dimensional confinement: Discrete versus continuous bond angles, J. Chem. Phys.
143, 243102 (2015).

3. Aiqun Huan, Walter Reisner, and Aniket Bhattacharya , Dynamics of DNA Squeezed inside a Nanochannel via a Sliding Gasket, Polymers 2016, 8 (10), 352;

4. Simon Bernier, Aiqun Huan, Walter Reisner, and Aniket Bhattacharya, Evolution of Nested Folding States in Compression of a Strongly Confined Semiflexible Chain Macromolecules 2018, 51 (11), 4012–4022