Force-extension Characteristics Research Articles

Coarse-grained modeling of DNA-RNA hybrids.

We introduce oxNA, a new model for the simulation of DNA-RNA hybrids that is based on two previously developed coarse-grained models-oxDNA and oxRNA. The model naturally reproduces the physical properties of hybrid duplexes, including their structure, persistence length, and force-extension characteristics. By parameterizing the DNA-RNA hydrogen bonding interaction, we fit the model's thermodynamic properties to experimental data using both average-sequence and sequence-dependent parameters. To demonstrate the model's applicability, we provide three examples of its use-calculating the free energy profiles of hybrid strand displacement reactions, studying the resolution of a short R-loop, and simulating RNA-scaffolded wireframe origami.

Comparison of the force deterioration of different orthodontic elastomeric materials in artificial saliva: An in vitro study

The orthodontist must be able to choose an elastic band with force-extension characteristics that are most suitable for the particular tooth movement required. From a clinician view it would be mandatory not only to know the clinical aspect of these elastics but also their basic properties, in order to extract the most out of these polymers. Stretching of elastics are thought to be the primary cause of force degradation of orthodontic elastics but there is evidence of increased force degradation of elastics when exposed to various types of substances like artificial saliva, phosphoric acid and citric acid. Orthodontic elastics have received mixed reactions of practitioners as reported by the vendors of orthodontic supplies. The present study is designed to compare the force deterioration of different orthodontic elastomeric materials in artificial saliva medium. There was a force deterioration over time in all materials, being greatest on the seventh day of the experiment, especially more in the chains; From the third to the fourth week there was no noticeable force degradation in either group; By the end of the experiment, modules showed less deterioration of the force compared to the chains and threads.

Modeling single molecule junction mechanics as a probe of interface bonding

Using the atomic force microscope based break junction approach, applicable to metal point contacts and single molecule junctions, measurements can be repeated thousands of times resulting in rich data sets characterizing the properties of an ensemble of nanoscale junction structures. This paper focuses on the relationship between the measured force extension characteristics including bond rupture and the properties of the interface bonds in the junction. A set of exemplary model junction structures has been analyzed using density functional theory based calculations to simulate the adiabatic potential surface that governs the junction elongation. The junction structures include representative molecules that bond to the electrodes through amine, methylsulfide, and pyridine links. The force extension characteristics are shown to be most effectively analyzed in a scaled form with maximum sustainable force and the distance between the force zero and force maximum as scale factors. Widely used, two parameter models for chemical bond potential energy versus bond length are found to be nearly identical in scaled form. Furthermore, they fit well to the present calculations of N–Au and S–Au donor-acceptor bonds, provided no other degrees of freedom are allowed to relax. Examination of the reduced problem of a single interface, but including relaxation of atoms proximal to the interface bond, shows that a single-bond potential form renormalized by an effective harmonic potential in series fits well to the calculated results. This allows relatively accurate extraction of the interface bond energy. Analysis of full junction models shows cooperative effects that go beyond the mechanical series inclusion of the second bond in the junction, the spectator bond that does not rupture. Calculations for a series of diaminoalkanes as a function of molecule length indicate that the most important cooperative effect is due to the interactions between the dipoles induced by the donor-acceptor bond formation at the junction interfaces. The force extension characteristic of longer molecules such as diaminooctane, where the dipole interaction effects drop to a negligible level, accurately fit to the renormalized single-bond potential form. The results suggest that measured force extension characteristics for single molecule junctions could be analyzed with a modified potential form that accounts for the energy stored in deformable mechanical components in series.

A comparison of orthodontic elastic forces: Focus on reduced inventory.

OBJECTIVES:To compare orthodontic elastics with different force extension characteristics, thereby aiming to reduce the orthodontist's inventory for elastics.MATERIALS AND METHODS:Thirty nonextraction class I models were used to determine extension distances. Light, medium, and heavy forced Latex elastics of size 1/4 and 3/16 (from three manufacturers) were used. Thirty elastics from each pack were selected, for a total sample size of 540 elastics. Elastic force was measured at three extensions: three times the lumen (A), first molar to opposing canine (B), and second molar to opposing canine distance (C). Force values were compared with the analysis of variance followed by the post hoc Scheffe test.RESULTS:Mean distance for extensions B and C were 22.3 and 38.7 mm, respectively. There was a continuous but significant increase in the force of 1/4 elastics when stretched from A to extension C. A significant increase in the force level of 3/16 elastics was only noted when stretched from A to B. Overall, 1/4 elastics had a wider range of force coverage in the extensions used, compared to 3/16 elastics.CONCLUSIONS:The use of 1/4 elastics is sufficient to cover the range of forces in orthodontic treatment.

Two-phase stretching of molecular chains.

Although stretching of most polymer chains leads to rather featureless force-extension diagrams, some, notably DNA, exhibit nontrivial behavior with a distinct plateau region. Here, we propose a unified theory that connects force-extension characteristics of the polymer chain with the convexity properties of the extension energy profile of its individual monomer subunits. Namely, if the effective monomer deformation energy as a function of its extension has a nonconvex (concave up) region, the stretched polymer chain separates into two phases: the weakly and strongly stretched monomers. Simplified planar and 3D polymer models are used to illustrate the basic principles of the proposed model. Specifically, we show rigorously that, when the secondary structure of a polymer is mostly caused by weak noncovalent interactions, the stretching is two phase, and the force-stretching diagram has the characteristic plateau. We then use realistic coarse-grained models to confirm the main findings and make direct connection to the microscopic structure of the monomers. We show in detail how the two-phase scenario is realized in the α-helix and DNA double helix. The predicted plateau parameters are consistent with single-molecules experiments. Detailed analysis of DNA stretching shows that breaking of Watson-Crick bonds is not necessary for the existence of the plateau, although some of the bonds do break as the double helix extends at room temperature. The main strengths of the proposed theory are its generality and direct microscopic connection.

Stretching-force–dependent transitions in single stranded DNA

Mechanical properties of DNA, in particular its stretch-dependent extension and loop formation properties, have been recognized as effective probes for understanding possible biochemical roles played by them in a living cell. Single stranded DNA (ssDNA), which till recently was presumed to be a simple flexible polymer continues to spring surprises. Synthetic ssDNA, like polydA (polydeoxyadenosines) have revealed an intriguing force-extension (FX) behavior exhibiting two plateaus, which is absent in polydT (polydeoxythymidines). Loop closing time in polydA had also been found to scale exponentially with inverse temperature, unexpected from generic models of homopolymers. Here we present a new model for polydA which incorporates both a helix-coil transition and an overstretching transition, accounting for the two plateaus. Using transfer matrix calculation and Monte Carlo simulation we show that the model reproduces different sets of experimental observations, namely FX characteristics and looping behavior, quantitatively. It also predicts a weak, nonmonotonic behavior in the temperature-extension characteristic of polydA.

The Processivity of Kinesin-2 Motors Suggests Diminished Front-Head Gating

Kinesin-2 motors, which are involved in intraflagellar transport and cargo transport along cytoplasmic microtubules, differ from motors in the canonical kinesin-1 family by having a heterodimeric rather than homodimeric structure and possessing a three amino acid insertion in their neck linker domain. To determine how these structural features alter the chemomechanical coupling in kinesin-2, we used single-molecule bead experiments to measure the processivity and velocity of mouse kinesin-2 heterodimer (KIF3A/B) and the engineered homodimers KIF3A/A and KIF3B/B and compared their behavior to Drosophila kinesin-1 heavy chain (KHC). Single-motor run lengths of kinesin-2 were 4-fold shorter than those of kinesin-1. Extending the kinesin-1 neck linker by three amino acids led to a similar reduction in processivity. Furthermore, kinesin-2 processivity varied inversely with ATP concentration. Stochastic simulations of the kinesin-1 and kinesin-2 hydrolysis cycles suggest that "front-head gating," in which rearward tension prevents ATP binding to the front head when both heads are bound to the microtubule, is diminished in kinesin-2. Because the mechanical tension that underlies front-head gating must be transmitted through the neck linker domains, we propose that the diminished coordination in kinesin-2 is a result of its longer and, hence, more compliant neck linker element.

Monte Carlo study of multiply crosslinked semiflexible polymer networks

We present a method to generate realistic, three-dimensional networks of crosslinked semiflexible polymers. The free energy of these networks is obtained from the force-extension characteristics of the individual polymers and their persistent directionality through the crosslinks. A Monte Carlo scheme is employed to obtain isotropic, homogeneous networks that minimize the free energy and for which all of the relevant parameters can be varied: the persistence length and the contour length as well as the crosslinking length may be chosen at will. We also provide an initial survey of the mechanical properties of our networks subjected to shear strains, showing them to display the expected nonlinear stiffening behavior. Also, a key role for nonaffinity and its relation to order in the network is uncovered.

Pulling Geometry-Induced Errors in Single Molecule Force Spectroscopy Measurements

In AFM-based single molecule force spectroscopy, it is tacitly assumed that the pulling direction coincides with the end-to-end vector of the molecule fragment being stretched. By systematically varying the position of the attachment point on the substrate relative to the AFM tip, we investigate empirically and theoretically the effect of the pulling geometry on force-extension characteristics of double-stranded DNA. We find that increasing the pulling angle can significantly lower the force of the characteristic overstretching transition and increase the width of the plateau feature beyond the canonical 70%. These effects, when neglected, can adversely affect the interpretation of measured force-extension relationships. We quantitatively evaluate force and extension errors originating from this “pulling angle effect” and stress the need to correct the pulling geometry when stretching rigid molecules with an AFM.

Nanoscale Mechanical Characterisation of Amyloid Fibrils Discovered in a Natural Adhesive

Using the atomic force microscope, we have investigated the nanoscale mechanical response of the attachment adhesive of the terrestrial alga Prasiola linearis (Prasiolales, Chlorophyta). We were able to locate and extend highly ordered mechanical structures directly from the natural adhesive matrix of the living plant. The in vivo mechanical response of the structured biopolymer often displayed the repetitive sawtooth force-extension characteristics of a material exhibiting high mechanical strength at the molecular level. Mechanical and histological evidence leads us to propose a mechanism for mechanical strength in our sample based on amyloid fibrils. These proteinaceous, pleated β-sheet complexes are usually associated with neurodegenerative diseases. However, we now conclude that the amyloid protein quaternary structures detected in our material should be considered as a possible generic mechanism for mechanical strength in natural adhesives.

Mechanism of RecA-mediated homologous recombination revisited by single molecule nanomanipulation

The mechanisms of RecA-mediated three-strand homologous recombination are investigated at the single-molecule level, using magnetic tweezers. Probing the mechanical response of DNA molecules and nucleoprotein filaments in tension and in torsion allows a monitoring of the progression of the exchange in real time, both from the point of view of the RecA-bound single-stranded DNA and from that of the naked double-stranded DNA (dsDNA). We show that strand exchange is able to generate torsion even along a molecule with freely rotating ends. RecA readily depolymerizes during the reaction, a process presenting numerous advantages for the cell's 'protein economy' and for the management of topological constraints. Invasion of an untwisted dsDNA by a nucleoprotein filament leads to an exchanged duplex that remains topologically linked to the exchanged single strand, suggesting multiple initiations of strand exchange on the same molecule. Overall, our results seem to support several important assumptions of the monomer redistribution model.

Modeling AFM-Induced PEVK Extension and the Reversible Unfolding of Ig/FNIII Domains in Single and Multiple Titin Molecules

Molecular elasticity is associated with a select number of polypeptides and proteins, such as titin, Lustrin A, silk fibroin, and spider silk dragline protein. In the case of titin, the globular (Ig) and non-globular (PEVK) regions act as extensible springs under stretch; however, their unfolding behavior and force extension characteristics are different. Using our time-dependent macroscopic method for simulating AFM-induced titin Ig domain unfolding and refolding, we simulate the extension and relaxation of hypothetical titin chains containing Ig domains and a PEVK region. Two different models are explored: 1) a series-linked WLC expression that treats the PEVK region as a distinct entropic spring, and 2) a summation of N single WLC expressions that simulates the extension and release of a discrete number of parallel titin chains containing constant or variable amounts of PEVK. In addition to these simulations, we also modeled the extension of a hypothetical PEVK domain using a linear Hooke's spring model to account for “enthalpic” contributions to PEVK elasticity. We find that the modified WLC simulations feature chain length compensation, Ig domain unfolding/refolding, and force-extension behavior that more closely approximate AFM, laser tweezer, and immunolocalization experimental data. In addition, our simulations reveal the following: 1) PEVK extension overlaps with the onset of Ig domain unfolding, and 2) variations in PEVK content within a titin chain ensemble lead to elastic diversity within that ensemble.

Calibration of force extension and force degradation characteristics of orthodontic latex elastics

The force-extension characteristics of orthodontic elastics made of natural rubber latex by 4 manufacturers were subjected to static testing under dry and wet conditions. The elastics consisted of 3 sizes: 3/16, 1/4, and 5/16 inch lumen sizes, each with forces specified according to the standard extension index of three times the lumen diameter. Most of the elastics did not match the specified index using the dry tests, but this should not be a serious clinical concern as all elastics showed acceptable regularity of force-extension characteristics. There was notable force degradation of all elastics when subject to water immersion, approximating 30% during the hour, but with an average less than 7% further loss up to 3 days. There were significant differences in force extension and force degradation characteristics between different extensions and force magnitudes for the elastics of the different manufacturers. It is suggested that the clinician could use the table of force degradation values for different extensions to select an appropriate elastic. (Am J Orthod Dentofacial Orthop 2000;118:280–7)

Pulling chromatin fibers: computer simulations of direct physical micromanipulations

A low-resolution molecular model, which combines the known mechanical properties of protein-free DNA with the accumulating picture of chromatosome structure, has been developed to account for the stretching of single chromatin fibers by an imposed external force. Force-extension characteristics of sets of chains accumulated by Monte Carlo sampling are consistent with recently observed findings in the non-destructive regime (<20 pN imposed force), where the structure of the chromatosome remains intact. The correspondence between simulation and the relaxation phase of the experiment limits the equilibrium entry-exit angle of linker DNA on the chromatosome to W=50(±10)° and the effective DNA linker length to L eff=40(±5) bp. The computed force-extension characteristics are relatively insensitive to other parameters of the model, precluding their accurate estimation. The introduction of an attractive potential between closely spaced nucleosomes reproduces the added initial resistance of single fibers to extension at high salt conditions. The consideration of elastic linkers also improves the fitting of assorted classical measurements of unstressed chromatin structure in solution. The overall picture of chromatin that emerges is an irregular, fluctuating, three-dimensional, zig-zag structure with intact, mechanically stable chromatosome units and deformable linkers. The modeled fiber undergoes large-scale configurational rearrangements without significant perturbation of the constituent chromatosome beads, collapsing into a highly condensed form in response to small (<2 kT) inter-nucleosomal attractions.

Development and Evaluation of a Biaxial Tensile Tester for Fabrics

Abstract At the Nonwovens Cooperative Research Center (NCRC), North Carolina State University, a prototype instrument has been designed to measure fabric behavior under biaxial force. The system is equipped with a segmented and self-adjusting clamping system designed to apply uniform finite strain in the sample without undesirable boundary effects. The control system is designed to allow tests to be performed under a constant force-ratio or a constant extension-ratio condition. The designs of the clamping and control systems of the instrument have been evaluated by testing a number of spunbonded nonwoven fabrics. The results show a significant influence of biaxial deformation on the force-extension characteristics of fabrics.

A program for developing a comprehensive mathematical description of the crossbridge cycle of muscle

We describe a computer modeling system for determining the changes of force, fraction of attached crossbridges, and crossbridge flux rate through a specifiable transition in response to length changes imposed on a crossbridge model of muscle. The crossbridge cycle is divided into multiple attached and detached states. The rates of transition from one state to another are defined by rate coefficients that can either be constant or vary with the position of the crossbridge relative to the thin-filament attachment site. This scheme leads to a system of differential equations defining the rates of change for the fractions of bridges in each state. Solutions for this system of equations are obtained at specified times during and after a length change using a method for systems with widely varying time constants (C. W. Gear, 1971, Numerical Initial Value Problems in Ordinary Differential Equations, Prentice-Hall, Englewood Cliffs, NJ). Crossbridges are divided into discrete populations that differ both in their axial displacement with respect to thin filament attachment sites and with respect to the twist of the actin helix. Separate solutions are made for the individual populations and are then averaged to obtain the ensemble response. Force is determined as the sum of the product of the force associated with each state multiplied by the fraction of bridges in that state. A measure of metabolic rate is determined as the net flux through one of the crossbridge transitions. When the force-extension characteristics of the individual crossbridges are linear and the filaments are noncompliant the fraction of attached bridges is equivalent to sarcomere stiffness. To illustrate the operation of the program, we also describe here some results obtained with a simplified scheme.

Effects of appliace size, arch wire diameter, and alloy composition on the in vitro delivery of the quad-helix appliace

The quad-helix appliace is a fixed lingual arch wire appliace that produces slow maxillary expansion for the treatment of maxillary constriction or crossbite in the primary and mixed dentitions. Despite considerable success in the clinical treatment of patients, there is little quantitative information about the force delivery of this appliace. The purpose of this investigation was to characterize the in vitro force delivery of the quad-helix appliance. Appliances of four sizes were fabricated from Elgiloy blue and stainless steel wires with diameters of 0.032, 0.036, and 0.038 inch. The force delivery in grams for 8-mm activation was determined from the force-extension characteristics using an Instron mechanical testing machine. The results show that the force delivery on the quad-helix appliace is affected significantly by changes in the appliance size and arch wire diameter, but is independent of alloy type (stainless steel of Elgiloy blue). The quantitative results from this investigation should provide worthwhile information for clinical appliance selection and treatment of patients with varying arch dimensions.

Force-extension characteristics of orthodontic elastics

The force-extension characteristics for a wide range of elastics were determined. It was found that (1) selection of elastics were determined. It was found that (1) selection of elastics based on 3 x lumen size will probably result in more force being generated than was previously reported, (2) there is very little difference seen in force-extension characteristics when the two manufacturers' elastics are compared, and (3) for experimental purposes, elastic testing can be done in the dry state for force-extension characteristic studies. This investigation has shown that stretching an orthodontic elastic to twice its original lumen diameter produces a force which better represents the manufacturer's expected value. Keeping these principles in mind, a more effective tooth-moving force can be realized, enabling the clinician to properly select orthodontic elastics for intra- and intermaxillary biomechanical procedures.

Stress-Strain Behavior of Natural Rubber Vulcanized in the Swollen State

Abstract Samples of natural rubber were vulcanized in the presence of n-decane, decalin and o-chlorobenzene. The diluents were then removed, and the force-extension characteristics of the samples studied over the range 1.1&amp;lt;α&amp;lt;2.0. The elastic behavior of the solution-vulcanized elastomers appear to be in much closer agreement with the statistical theory of elasticity than is the case for vulcanizates prepared in the dry state.

Stress-strain behaviour of natural rubber vulcanized in the swollen state

Samples of natural rubber were vulcanized in the presence of n-decane, decalin and o-chlorobenzene. The diluents were then removed, and the force-extension characteristics of the samples studied over the range 1·1 < α < 2·0. The elastic behaviour of the solution-vulcanized elastomers appear to be in much closer agreement with the statistical theory of elasticity than is the case for vulcanizates prepared in the dry state.