DNA denaturation bubbles: free-energy landscape and nucleation/closure rates

The issue of the nucleation and slow closure mechanisms of non superhelical stress-induced denaturation bubbles in DNA is tackled using coarse-grained MetaDynamics and Brownian simulations. A minimal mesoscopic model is used where the double helix is made of two interacting bead-spring rotating strands with a prescribed torsional modulus in the duplex state. We demonstrate that timescales for the nucleation (resp. closure) of an approximately 10 base-pair bubble, in agreement with experiments, are associated with the crossing of a free-energy barrier of $22~k_{\rm B}T$ (resp. $13~k_{\rm B}T$) at room temperature $T$. MetaDynamics allows us to reconstruct accurately the free-energy landscape, to show that the free-energy barriers come from the difference in torsional energy between the bubble and duplex states, and thus to highlight the limiting step, a collective twisting, that controls the nucleation/closure mechanism, and to access opening time scales on the millisecond range. Contrary to small breathing bubbles, these more than 4~base-pair bubbles are of biological relevance, for example when a preexisting state of denaturation is required by specific DNA-binding proteins.Comment: 11 pages (5 pages and Appendix), 13 figures, published in Journal of Chemical Physic

Energy required to pinch a DNA plectoneme

DNA supercoiling plays an important role on a biological point of view. One of its consequences at the supra-molecular level is the formation of DNA superhelices named plectonemes. Normally separated by a distance on the order of 10 nm, the two opposite double-strands of a DNA plectoneme must be brought closer if a protein or protein complex implicated in genetic regulation is to be bound simultaneously to both strands, as if the plectoneme was locally pinched. We propose an analytic calculation of the energetic barrier, of elastic nature, required to bring closer the two loci situated on the opposed double-strands. We examine how this energy barrier scales with the DNA supercoiling. For physically relevant values of elastic parameters and of supercoiling density, we show that the energy barrier is in the $k_{\rm B} T$ range under physiological conditions, thus demonstrating that the limiting step to loci encounter is more likely the preceding plectoneme slithering bringing the two loci side by side.Comment: Published version (new title to conform to editorial policy

Mixed lipid bilayers with locally varying spontaneous curvature and bending

A model of lipid bilayers made of a mixture of two lipids with different average compositions on both leaflets, is developed. A Landau hamiltonian describing the lipid-lipid interactions on each leaflet, with two lipidic fields $\psi_1$ and $\psi_2$, is coupled to a Helfrich one, accounting for the membrane elasticity, via both a local spontaneous curvature, which varies as $C_0+C_1(\psi_1-\psi_2)/2$, and a bending modulus equal to $\kappa_0+\kappa_1(\psi_1+\psi_2)/2$. This model allows us to define curved patches as membrane domains where the asymmetry in composition, $\psi_1-\psi_2$, is large, and thick and stiff patches where $\psi_1+\psi_2$ is large. These thick patches are good candidates for being lipidic rafts, as observed in cell membranes, which are composed primarily of saturated lipids forming a liquid-ordered domain and are known to be thick and flat nano-domains. The lipid-lipid structure factors and correlation functions are computed for globally spherical membranes and planar ones. Phase diagrams are established, within a Gaussian approximation, showing the occurrence of two types of Structure Disordered phases, with correlations between either curved or thick patches, and an Ordered phase, corresponding to the divergence of the structure factor at a finite wave vector. The varying bending modulus plays a central role for curved membranes, where the driving force $\kappa_1C_0^2$ is balanced by the line tension, to form raft domains of size ranging from 10 to 100~nm. For planar membranes, raft domains emerge via the cross-correlation with curved domains. A global picture emerges from curvature-induced mechanisms, described in the literature for planar membranes, to coupled curvature- and bending-induced mechanisms in curved membranes forming a closed vesicle

Inwardly curved polymer brushes : Concave is not like Convex

Inwardly curved polymer brushes are present in cylindrical and spherical micelles or in membranes tubes and vesicles decorated with anchored polymers, and influence their stability. We consider such polymer brushes in good solvent and show that previous works, based on a self-similar concentric structure of the brush, are physically inconsistent. We use scaling laws to derive very simply the leading term of the free energy in the high curvature limit, where the osmotic pressure is the relevant physical ingredient. We also derive the complete conformation at all curvatures using a self-consistent field approach. The free energy is computed therefrom using a local scaling description.Comment: Subm. to Eur. Phys. J. E., rev. version, 12 pages plus 9 figures, PACS : 36.20.Ey / 82.35.Gh / 82.70.-y. Figure 1 modified. In introduction, discussion added on concentration gradients near the edge of the brush. [email protected] [email protected] [email protected] [email protected]