Elastic rod model of a supercoiled DNA molecule

We study the elastic behaviour of a supercoiled DNA molecule. The simplest model is that of a rod-like chain, involving two elastic constants, the bending and the twist rigidities. Writing this model in terms of Euler angles, we show that the corresponding Hamiltonian is singular and needs a small distance cut-off, which is a natural length scale giving the limit of validity of the model, of the order of the double-helix pitch. The rod-like chain in the presence of the cut-off is able to reproduce quantitatively the experimentally observed effects of supercoiling on the elongation-force characteristics, in the small supercoiling regime. An exact solution of the model, using both transfer matrix techniques and its mapping to a quantum mechanics problem, allows to extract, from the experimental data, the value of the twist rigidity. We also analyse the variation of the torque and the writhe-to-twist ratio versus supercoiling, showing analytically the existence of a rather sharp crossover regime which can be related to the excitation of plectoneme-like structures. Finally we study the extension fluctuations of a stretched and supercoiled DNA molecule, both at fixed torque and at fixed supercoiling angle, and we compare the theoretical predictions to some preliminary experimental data. Received 1 April 1999 and Received in final form 4 January 2000     

Influences of flexible defect on the interplay of supercoiling and knotting of circular DNA

Knots are discovered in biophysical systems, such as DNA and proteins. Knotted portions in knotted DNA are significantly bent and their corresponding bending angles are comparable with or larger than the sharp bending angle resulting in flexible defects. The role of flexible defects in the interplay of supercoiling and knotting of circular DNA were predicted by a Monte Carlo simulation. In knotted DNA with a particular knot type, a flexible defect noticeably enhances the supercoiling of the knotted DNA and the decreasing excitation energy makes the knotted portion more compact. A reduction in twist rigidity and unwinding of flexible defects are incorporated into the numerical simulations, so that interplay of supercoiling and knotting of circular DNA is studied under torsional conditions. Increasing unwinding not only results in a wider linking number distribution, but also leads to a drift of the distribution to lower values. A flexible defect has obvious effects on knotting probability. The summation of equilibrium distribution probability for nontrivial knotted DNA with different contour length does not change with excitation energy monotonically and has a maximum at an intermediate value of excitation energy around 5 kBT. In the phase space of knot length and gyration radius of knotted DNA, knot length does not anticorrelate with its gyration radius, which is attributed to the flexible defect in the knotted portion, which leads to the release of bending energy and inhibited the competition between entropy and bending energy.     

Supercoiling induces denaturation bubbles in circular DNA

We present a theoretical framework for the thermodynamic properties of supercoiling-induced denaturation bubbles in circular double-stranded DNA molecules. We explore how DNA supercoiling, ambient salt concentration, and sequence heterogeneity impact on the bubble occurrence. An analytical derivation of the probability distribution to find multiple bubbles is derived and the relevance for supercoiled DNA discussed. We show that in?vivo sustained DNA bubbles are likely to occur due to partial twist release in regions rich in weaker AT base pairs. Single DNA plasmid imaging experiments clearly demonstrate the existence of bubbles in free solution.     

Supercoiling and denaturation of DNA loops

We study the statistical mechanics of small DNA loops emphasizing the competition between elasticity, supercoiling, and denaturation. Motivated by recent experiments and atomistic molecular dynamics simulation, we propose a new coarse-grained phenomenological model of DNA. We extend the classical elastic rod models to include the possibility of denaturation and nonlinear twist elasticity. Using this coarse-grained model, we obtain a phase diagram in terms of fractional overtwist and loop size that can be used to rationalize a number of experimental results which have also been confirmed by atomistic simulations.     

Elasticity theory of a twisted stack of plates

We present an elastic model of B-form DNA as a stack of thin, rigid plates or base pairs that are not permitted to deform. The symmetry of DNA and the constraint of plate rigidity limit the number of bulk elastic constants contributing to a macroscopic elasticity theory of DNA to four. We derive an effective twist-stretch energy in terms of the macroscopic stretch along and relative excess twist about the DNA molecular axis. In addition to the bulk stretch and twist moduli found previously, we obtain a twist-stretch modulus with the following remarkable properties: 1) it vanishes when the radius of the helical curve following the geometric center of each plate is zero, 2) it vanishes with the elastic constant K₂₃ that couples compression normal to the plates to a shear strain, if the plates are perpendicular to the molecular axis, and 3) it is nonzero if the plates are tilted relative to the molecular axis. This implies that a laminated helical structure carved out of an isotropic elastic medium will not twist in response to a stretching force, but an isotropic material will twist if it is bent into the shape of a helix. Received: 4 July 1997 / Received in final form: 16 October 1997 / Accepted: 21 October 1997     

Physical Approaches to the Study of DNA

New micromanipulation techniques now enable physicists and biologists to study the behavior of single biomolecules such as DNA. In particular, it is possible to measure the elastic response of individual DNA molecules to changes in the double helix's supercoiling. The force versus extension diagram for torsionally relaxed DNA is continuous and allows one to evaluate the persistence length of the polymer. When the molecule is supercoiled, however, stretching leads to the buildup of torsional stress in the double helix's axis. When the twist energy thus generated increases beyond a critical value, the molecule is locally destabilized and changes conformation. This structural transition occurs at stretching forces which can be exerted in vivo by molecular motors and at degrees of supercoiling found in the cell, and may have implications for DNA structure and function within the nucleus.     

受拉扭弹性细杆超螺旋形态的定性分析

基于弹性杆的Kirchhoff模型讨论受拉扭弹性细杆的超螺旋形态.导出细长螺旋杆的等效抗弯和抗扭刚度.分析受拉扭弹性细杆的稳定性和分岔,且利用等效刚度概念将弹性杆的稳定性条件应用于对细长螺旋杆稳定性的判断.在扭矩不变条件下增加拉力至极限值时,直杆平衡状态失稳转为螺旋杆状态.继续增加拉力,直螺旋杆平衡状态失稳卷绕为超螺旋杆.从而对Thompson/Champney实验中受拉扭弹性细杆形成超螺旋形态的多次卷绕现象作出定性的理论解释. 关键词： 弹性细杆 Kirchhoff动力学比拟 等效刚度 超螺旋形态     

Twisted protein aggregates and disease: the stability of sickle hemoglobin fibers

We describe how twist could play an essential role in stabilizing 20 nm diameter sickle hemoglobin fibers. Our theory successfully reproduces the observed variation of helical pitch length with fiber diameter. With no remaining adjustable parameters it also yields a prediction for the torsional rigidity of sickle hemoglobin fibers that is in good agreement with experiment and hence retains the striking feature that such fibers can be highly mechanically anisotropic, even with a ratio of bending to torsional rigidity of about 50. We discuss how our study might be relevant to the development of treatment strategies.     

Stretching instability of helical springs

We show that when a gradually increasing tensile force is applied to the ends of a helical spring with sufficiently large ratios of radius to pitch and twist to bending rigidity, the end-to-end distance undergoes a sequence of discontinuous stretching transitions. Subsequent decrease of the force leads to steplike contraction, and hysteresis is observed. For finite helices, the number of these transitions increases with the number of helical turns but only one stretching and one contraction instability survive in the limit of an infinite helix. We calculate the critical line that separates the region of parameters in which the deformation is continuous from that in which stretching instabilities occur.     

Finite-width corrections to the Nambu action for the Nielsen-Olesen string

The finite-width correction terms to the Nambu action for Nielsen-Olesen strings are calculated. They consist of an extrinsic curvature squared or rigidity term and a new “twist” term. The extrinsic curvature term prevents cusps forming, rounding them off with a curvature radius of the order of the string width.     

PROPAGATION OF TWIST SOLITONS IN FULLY INHOMOGENEOUS DNA CHAINS

In the framework of a recently introduced model of DNA torsional dynamics, we argued — on the basis of perturbative considerations — that an inhomogeneous DNA chain could support long-lived soliton-type excitations due to the peculiar geometric structure of DNA and the effect of this on nonlinear torsional dynamics. Here we consider an inhomogeneous version of this model of DNA torsional dynamics, and investigate numerically the propagation of solitons in a DNA chain with a real base sequence (corresponding to the Human Adenovirus 2); this implies inhomogeneities of up to 50% in the base masses and inter-pair interactions. We find that twist solitons propagate for considerable distances (2–10 times their diameters) before stopping due to phonon emission. Our results show that twist solitons may exist in realistic DNA chain models, and on a more general level that solitonic propagation can take place in highly inhomogeneous media. The most relevant feature for general nonlinear dynamics is that we identify the physical mechanisms allowing this behavior and thus the class of models candidate to support long-lived soliton-type excitations in the presence of significant inhomogeneities.     

Analytical description of extension, torque, and supercoiling radius of a stretched twisted DNA

We study the mixture of extended and supercoiled DNA that occurs in a twisted DNA molecule under tension. Closed-form asymptotic solutions for the supercoiling radius, extension, and torque of the molecule are obtained in the high-force limit where electrostatic and elastic effects dominate. We demonstrate that experimental data obey the extension and torque scaling laws apparent in our formulas, in the regime where thermal fluctuation effects are quenched by applied force.     

Elastic response of single DNA molecules exhibits a reentrant collapsing transition

We measured the elastic response of single DNA molecules at various concentrations of the trivalent cation, spermidine. When added spermidine caused the DNA to collapse, the force-extension curves showed either plateaus or stick-release patterns depending on the concentration. The periodic stick-release response determines a characteristic length, which may reflect toroidal supercoiling. At high concentrations of spermidine, we observed the reelongation of single molecules of collapsed DNA. Thus condensation occurs between lower and upper critical concentrations, verifying that the transition is reentrant as theoretically predicted.     

Thermal Vibration and Twist Induced Semiconducting Behaviour in Short DNA Wires

We study the transport properties of electrons in a short homogeneous DNA molecule where thermal vibrations and twist fluctuations of the base molecules are considered. The nonlinear current-voltage curves can be derived by using the equivalent single-particle multichannel network. The voltage gap is sensitive to the strength of thermal vibrations and twist fluctuations of the base molecules. Our results are in good agreement with the recent finding of semiconducting behaviour in short poly（G）-poly（C） DNA oligomers. The present method can also be used to calculate the other molecular wires.     

Torsional elastic deformations of microtubules within continuous sheet model

This paper develops a rigorous analysis of the microtubule elastic deformations in terms of the torsional degrees of freedom using the helix-based cylindrical structure of this biopolymer. Methods of differential geometry and the theory of elasticity are employed in our analysis. We find equilibrium conditions and constitutive equations in the linear regime. We estimate the value of torsional rigidity for microtubules based on their structure and some experimentally known elastic properties. The paper concludes with the derivation of a bulk modulus formula for a microtubule in solution. Both the entropy change and the fluctuation of the twist angle are obtained.     

A geometrical template for toroidal aggregates of chiral macromolecules

The formation of toroidal aggregates by long chiral molecules of biological origin, as collagen, f-actin and DNA, or by chiral synthetic polypeptides has been observed in specific ionic environments. Such aggregates have received considerable attention in order to identify the various physical factors susceptible to contribute to this original morphogenesis, particularly in the case of those formed by DNA. We consider here the eventual role of a spontaneous uniform twist of micrometric pitch whose possible occurrence is suggested by some observations and by recent studies of DNA dense phases exhibiting cholesteric and “blue” phase structures. Following an approach inspired by the geometry and topology of fiber bundles, we show that the necessity to propagate such a twist in a dense bundle of fibers leads to the formation of aggregates having a toroidal shape and, in the case of the nanometric aggregates of DNA, characteristic sizes similar to those observed.     

Role of tension and twist in single-molecule DNA condensation

Using magnetic tweezers, we study in real time the condensation of single DNA molecules under tension. We find that DNA condensation occurs via discrete nucleated events. By measuring the influence of an imposed twist, we show that condensation is initiated by the formation of a plectonemic supercoil. This demonstrates a strong interplay between the condensation transition and externally imposed mechanical constraints.     

一种改进型单分子操纵装置及其应用

改进了单分子横向磁镊装置,可以直接用于观察单个DNA分子的伸长和扭转并随时更换样品池内的溶液,还可以同时操纵多个DNA分子,大大提高实验效率.此方法可以提供01到40pN范围的拉力,足以满足大部分单分子DNA实验的要求.用该装置实时观测到了DNA分子在拉力作用下的伸长以及在旋转磁场作用下的扭转,并成功地观察到了分子马达拉动DNA的动力学过程,从而验证了该装置的实用性. 关键词： 横向磁镊 单分子操纵 DNA拉伸 DNA扭转     

Molecular elasticity and the geometric phase

We present a method for solving the wormlike-chain (WLC) model for twisting semiflexible polymers to any desired accuracy. We show that the WLC free energy is a periodic function of the applied twist with period 4pi. We develop an analogy between WLC elasticity and the geometric phase of a spin-1 / 2 system. These analogies are used to predict elastic properties of twist-storing polymers. We graphically display the elastic response of a single molecule to an applied torque. This study is relevant to mechanical properties of biopolymers such as DNA.     

Thermomechanics of DNA: theory of thermal stability under load

A theory for thermomechanical behavior of homogeneous DNA at thermal equilibrium predicts critical temperatures for denaturation under torque and stretch, phase diagrams for stable B-DNA, supercoiling, optimally stable torque, and the overstretching transition as force-induced DNA melting. Agreement with available single molecule manipulation experiments is excellent.