Papers by Nicolas Destainville
The Journal of Physical Chemistry B, 2016
Cell membranes are out of thermodynamic equilibrium notably because of membrane recycling, i.e., ... more Cell membranes are out of thermodynamic equilibrium notably because of membrane recycling, i.e., active exchange of material with the cytosol. We propose an analytically tractable model of biomembrane predicting the effects of recycling on the size of protein nanodomains also called protein clusters. The model includes a short-range attraction between proteins and a weaker long-range repulsion which ensures the existence of so-called cluster phases in equilibrium, where monomeric proteins coexist with finite-size domains. Our main finding is that, when taking recycling into account, the typical cluster size at steady state increases logarithmically with the recycling rate at fixed protein concentration. Using physically realistic model parameters, the predicted 2-fold increase due to recycling in living cells is most likely experimentally measurable with the help of super-resolution microscopy.
Journal of Statistical Physics, Sep 1, 2005
We perform numerical studies including Monte Carlo simulations of high rotational symmetry random... more We perform numerical studies including Monte Carlo simulations of high rotational symmetry random tilings. For computational convenience, our tilings obey fixed boundary conditions in regular polygons. Such tilings are put in correspondence with algorithms for sorting lists in computer science. We obtain statistics on path counting and vertex coordination which compare well with predictions of mean-field theory and allow estimation of the configurational entropy, which tends to the value 0.568 per vertex in the limit of continuous symmetry. Tilings with phason strain appear to share the same entropy as unstrained tilings, as predicted by mean-field theory. We consider the thermodynamic limit and argue that the limiting fixed boundary entropy equals the limiting free boundary entropy, although these differ for finite rotational symmetry.
Biophys J, Mar 10, 2009
By exploring a recent model [Palmeri, J., M. Manghi, and N. Destainville. 2007. Phys. Rev. Lett. ... more 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.
We propose the first algebraic determinantal formula to enumerate random rhombus tilings filling ... more We propose the first algebraic determinantal formula to enumerate random rhombus tilings filling a centro-symmetric octagon of any size. This result uses the Gessel-Viennot technique and generalizes to any octagon a former specialized formula by Elnitsky.
Biophysical Journal, 2005
Single molecule tracking is a powerful way to look at the dynamic organization of plasma membrane... more Single molecule tracking is a powerful way to look at the dynamic organization of plasma membranes. However there are some limitations to its use. For example, it was recently observed (1), using numerical simulation, that time-averaging effects inherent to the exposure time of detectors are likely to bias the apparent motion of molecules confined in microdomains. Here, we solve this apparently limiting issue analytically. We explore this phenomenon by calculating its effects on the observed diffusion coefficients and domain sizes. We demonstrate that the real parameters can be easily recovered from the measured apparent ones. Interestingly, we find that single molecule tracking can be used to explore events occurring at a time scale smaller than the exposure time.
Statistical DNA models available in the literature are often effective models where the base-pair... more 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.
Journal of Statistical Physics, Apr 10, 2000
Some combinatorial properties of fixed boundary rhombus random tilings with octagonal symmetry ar... more Some combinatorial properties of fixed boundary rhombus random tilings with octagonal symmetry are studied. A geometrical analysis of their configuration space is given as well as a description in terms of discrete dynamical systems, thus generalizing previous results on the more restricted class of codimension-one tilings. In particular this method gives access to counting formulas, which are directly related to questions of entropy in these statistical systems. Methods and tools from the field of enumerative combinatorics are used.
We develop further a statistical model coupling denaturation and chain conformations in DNA (Palm... more We develop further a statistical model coupling denaturation and chain conformations in DNA (Palmeri J, Manghi M and Destainville N 2007 Phys. Rev. Lett. 99 088103). Our Discrete Helical Wormlike Chain model takes explicitly into account the three elastic degrees of freedom, namely stretching, bending and torsion of the polymer. By integrating out these external variables, the conformational entropy contributes to bubble nucleation (opening of base-pairs), which sheds light on the DNA melting mechanism. Because the values of monomer length, bending and torsional moduli differ significantly in dsDNA and ssDNA, these effects are important. Moreover, we explore in this context the role of an additional loop entropy and analyze finite-size effects in an experimental context where polydA-polydT is clamped by two G-C strands, as well as for free polymers.
Biophysical Journal, 2016
Physical Review Letters, Jun 25, 2010
We build a quantum algorithm which uses the Grover quantum search procedure in order to sample th... more We build a quantum algorithm which uses the Grover quantum search procedure in order to sample the exact equilibrium distribution of a wide range of classical statistical mechanics systems. The algorithm is based on recently developed exact Monte Carlo sampling methods, and yields a polynomial gain compared to classical procedures.
We propose an exact technique to calculate lower bounds of spectral gaps of discrete time reversi... more We propose an exact technique to calculate lower bounds of spectral gaps of discrete time reversible Markov chains on finite state sets. Spectral gaps are a common tool for evaluating convergence rates of Markov chains. As an illustration, we successfully use this technique to evaluate the "absorption time" of the "Backgammon model", a paradigmatic model for glassy dynamics. We also discuss the application of this technique to the "Contingency table problem", a notoriously difficult problem from probability theory. The interest of this technique is that it connects spectral gaps, which are quantities related to dynamics, with static quantities, calculated at equilibrium.
Langmuir, 2010
The statistical physics and dynamics of double supported bilayers are studied theoretically. The ... more The statistical physics and dynamics of double supported bilayers are studied theoretically. The main goal in designing double supported lipid bilayers is to obtain model systems of biomembranes: the upper bilayer is meant to be almost freely floating, the substrate being screened by the lower bilayer. The fluctuation-induced repulsion between membranes and between the lower membrane and the wall are explicitly taken into account using a Gaussian variational approach. It is shown that the variational parameters, the "effective" adsorption strength and the average distance to the substrate, depend strongly on temperature and membrane elastic moduli, the bending rigidity and the microscopic surface tension, which is a signature of the crucial role played by membrane fluctuations. The range of stability of these supported membranes is studied, showing a complex dependence on bare adsorption strengths. In particular, the experimental conditions to have an upper membrane slightly perturbed by the lower one and still bound to the surface are found. Included in the theoretical calculation of the damping rates associated with membrane normal modes are hydrodynamic friction by the wall and hydrodynamic interactions between both membranes.
Current topics in membranes, 2016
For several decades, the phenomenon of membrane component segregation into microdomains has been ... more For several decades, the phenomenon of membrane component segregation into microdomains has been a well-known and highly debated subject, and varying concepts including the raft hypothesis, the fence-and-picket model, hydrophobic-mismatch, and specific protein-protein interactions have been offered as explanations. Here, we review the level of insight into the molecular architecture of membrane domains one is capable of obtaining through biological experimentation. Using SNARE proteins as a paradigm, comprehensive data suggest that several dozens of molecules crowd together into almost circular spots smaller than 100 nm. Such clusters are highly dynamical as they constantly capture and lose molecules. The organization has a strong influence on the functional availability of proteins and likely provides a molecular scaffold for more complex protein networks. Despite this high level of insight, fundamental open questions remain, applying not only to SNARE protein domains but more gene...
Physical Review B Condensed Matter, Mar 12, 2003
We analyze the spreading of wave packets in two-dimensional quasiperiodic and random tilings as a... more We analyze the spreading of wave packets in two-dimensional quasiperiodic and random tilings as a function of their codimension, i.e., of their topological complexity. In the quasiperiodic case, we show that the diffusion exponent that characterizes the propagation decreases when the codimension increases and goes to 1/2 in the high codimension limit. By contrast, the exponent for the random tilings is independent of their codimension and also equals 1/2. This shows that, in high codimension, the quasiperiodicity is irrelevant and that the topological disorder leads in every case, to a diffusive regime, at least in the time scale investigated here.
Two-dimensional random tilings of rhombi can be seen as projections of two-dimensional membranes ... more Two-dimensional random tilings of rhombi can be seen as projections of two-dimensional membranes embedded in hypercubic lattices of higher dimensional spaces. Here, we consider tilings projected from a D-dimensional space. We study the limiting case, when the quantity D, and therefore the number of different species of tiles, become large. We had previously demonstrated [1] that, in this limit, the thermodynamic properties of the tiling become independent of the boundary conditions. The exact value of the limiting entropy and finite D corrections remain open questions. Here, we develop a meanfield theory, which uses an iterative description of the tilings based on an analogy with avoiding oriented walks on a random tiling. We compare the quantities so-obtained with numerical calculations. We also discuss the role of spatial correlations.
Single molecule experiments on B-DNA stretching have revealed one or two structural transitions, ... more Single molecule experiments on B-DNA stretching have revealed one or two structural transitions, when increasing the external force. They are characterized by a sudden increase of DNA contour length and a decrease of the bending rigidity. It has been proposed that the first transition, at forces of 60--80 pN, is a transition from B to S-DNA, viewed as a stretched duplex DNA, while the second one, at stronger forces, is a strand peeling resulting in single stranded DNAs (ssDNA), similar to thermal denaturation. But due to experimental conditions these two transitions can overlap, for instance for poly(dA-dT). We derive analytical formula using a coupled discrete worm like chain-Ising model. Our model takes into account bending rigidity, discreteness of the chain, linear and non-linear (for ssDNA) bond stretching. In the limit of zero force, this model simplifies into a coupled model already developed by us for studying thermal DNA melting, establishing a connexion with previous fitting parameter values for denaturation profiles. We find that: (i) ssDNA is fitted, using an analytical formula, over a nanoNewton range with only three free parameters, the contour length, the bending modulus and the monomer size; (ii) a surprisingly good fit on this force range is possible only by choosing a monomer size of 0.2 nm, almost 4 times smaller than the ssDNA nucleobase length; (iii) mesoscopic models are not able to fit B to ssDNA (or S to ss) transitions; (iv) an analytical formula for fitting B to S transitions is derived in the strong force approximation and for long DNAs, which is in excellent agreement with exact transfer matrix calculations; (v) this formula fits perfectly well poly(dG-dC) and $\lambda$-DNA force-extension curves with consistent parameter values; (vi) a coherent picture, where S to ssDNA transitions are much more sensitive to base-pair sequence than the B to S one, emerges.
Nucleic acids research, Jan 12, 2015
Being capable of characterizing DNA local bending is essential to understand thoroughly many biol... more Being capable of characterizing DNA local bending is essential to understand thoroughly many biological processes because they involve a local bending of the double helix axis, either intrinsic to the sequence or induced by the binding of proteins. Developing a method to measure DNA bend angles that does not perturb the conformation of the DNA itself or the DNA-protein complex is a challenging task. Here, we propose a joint theory-experiment high-throughput approach to rigorously measure such bend angles using the Tethered Particle Motion (TPM) technique. By carefully modeling the TPM geometry, we propose a simple formula based on a kinked Worm-Like Chain model to extract the bend angle from TPM measurements. Using constructs made of 575 base-pair DNAs with in-phase assemblies of one to seven 6A-tracts, we find that the sequence CA6CGG induces a bend angle of 19° ± 4°. Our method is successfully compared to more theoretically complex or experimentally invasive ones such as cyclizati...
The European physical journal. E, Soft matter, 2014
A model of lipid bilayers made of a mixture of two lipids with different average compositions on ... more 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 ψ 1 and ψ 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(ψ 1 - ψ 2/2), and a bending modulus equal to κ 0 + κ 1(ψ 1 + ψ 2)/2. This model allows us to define curved patches as membrane domains where the asymmetry in composition, ψ 1 - ψ 2, is large, and thick and stiff patches where ψ 1 + ψ 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 and for a whole set of par...
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Papers by Nicolas Destainville