Thermal denaturation of fluctuating finite DNA chains: the role of bending rigidity in bubble nucleation

Statistical DNA models available in the literature are often effective models where the base-pair state only (unbroken or broken) is considered. Because of a decrease by a factor of 30 of the effective bending rigidity of a sequence of broken bonds, or bubble, compared to the double stranded state, the inclusion of the molecular conformational degrees of freedom in a more general mesoscopic model is needed. In this paper we do so by presenting a 1D Ising model, which describes the internal base pair states, coupled to a discrete worm like chain model describing the chain configurations [J. Palmeri, M. Manghi, and N. Destainville, Phys. Rev. Lett. 99, 088103 (2007)]. This coupled model is exactly solved using a transfer matrix technique that presents an analogy with the path integral treatment of a quantum two-state diatomic molecule. When the chain fluctuations are integrated out, the denaturation transition temperature and width emerge naturally as an explicit function of the model parameters of a well defined Hamiltonian, revealing that the transition is driven by the difference in bending (entropy dominated) free energy between bubble and double-stranded segments. The calculated melting curve (fraction of open base pairs) is in good agreement with the experimental melting profile of polydA-polydT. The predicted variation of the mean-square-radius as a function of temperature leads to a coherent novel explanation for the experimentally observed thermal viscosity transition. Finally, the influence of the DNA strand length is studied in detail, underlining the importance of finite size effects, even for DNA made of several thousand base pairs.Comment: Latex, 28 pages pdf, 9 figure

Ionic Capillary Evaporation in Weakly Charged Nanopores

Using a variational field theory, we show that an electrolyte confined to a neutral cylindrical nanopore traversing a low dielectric membrane exhibits a first-order ionic liquid-vapor pseudo-phase-transition from an ionic-penetration "liquid" phase to an ionic-exclusion "vapor" phase, controlled by nanopore-modified ionic correlations and dielectric repulsion. For weakly charged nanopores, this pseudotransition survives and may shed light on the mechanism behind the rapid switching of nanopore conductivity observed in experiments.Comment: This version is accepted for publication in PR

Competition between Born solvation, dielectric exclusion, and Coulomb attraction in spherical nanopores

The recent measurement of a very low dielectric constant, $\epsilon$, of water confined in nanometric slit pores leads us to reconsider the physical basis of ion partitioning into nanopores. For confined ions in chemical equilibrium with a bulk of dielectric constant $\epsilon_b>\epsilon$, three physical mechanisms, at the origin of ion exclusion in nanopores, are expected to be modified due to this dielectric mismatch: dielectric exclusion at the water-pore interface (with membrane dielectric constant, $\epsilon_m<\epsilon$), the solvation energy related to the difference in Debye-H\"uckel screening parameters in the pore, $\kappa$, and in the bulk $\kappa_b$, and the classical Born solvation self-energy proportional to $\epsilon^{-1}-\epsilon_b^{-1}$. Our goal is to clarify the interplay between these three mechanisms and investigate the role played by the Born contribution in ionic liquid-vapor (LV) phase separation in confined geometries. We first compute analytically the potential of mean force (PMF) of an ion of radius $R_i$ located at the center of a nanometric spherical pore of radius $R$. Computing the variational grand potential for a solution of confined ions, we then deduce the partition coefficients of ions in the pore. Phase diagrams of the LV transition are established for various parameter values and we show that a signature of this phase transition can be detected by monitoring the total osmotic pressure. For charged nanopores, these exclusion effects compete with the electrostatic attraction that imposes the entry of counterions into the pore to enforce electro-neutrality. This study will therefore help in deciphering the respective roles of the Born self-energy and dielectric mismatch in experiments and simulations of ionic transport through nanopores.Comment: Supplemental Material on deman

Microscopic mechanism for experimentally observed anomalous elasticity of DNA in 2D

By exploring a recent model [Palmeri, J., M. Manghi, and N. Destainville. 2007. Phys. Rev. Lett. 99:088103] where DNA bending elasticity, described by the wormlike chain model, is coupled to base-pair denaturation, we demonstrate that small denaturation bubbles lead to anomalies in the flexibility of DNA at the nanometric scale, when confined in two dimensions (2D), as reported in atomic force microscopy (AFM) experiments [Wiggins, P. A., et al. 2006. Nature Nanotech. 1:137-141]. Our model yields very good fits to experimental data and quantitative predictions that can be tested experimentally. Although such anomalies exist when DNA fluctuates freely in three dimensions (3D), they are too weak to be detected. Interactions between bases in the helical double-stranded DNA are modified by electrostatic adsorption on a 2D substrate, which facilitates local denaturation. This work reconciles the apparent discrepancy between observed 2D and 3D DNA elastic properties and points out that conclusions about the 3D properties of DNA (and its companion proteins and enzymes) do not directly follow from 2D experiments by AFM.Comment: To appear in Biophys. J. 8 pages, supplementary information included (7 pages