Characterizing titin's I-band Ig domain region as an entropic spring

1998 ◽  
Vol 111 (11) ◽  
pp. 1567-1574 ◽  
Author(s):  
W.A. Linke ◽  
M.R. Stockmeier ◽  
M. Ivemeyer ◽  
H. Hosser ◽  
P. Mundel
Keyword(s):  
Muscle Protein ◽  
Persistence Length ◽  
Thick Filament ◽  
Contour Length ◽  
Chain Model ◽  
Bending Rigidity ◽  
Force Extension ◽  
Average Force ◽  
Wormlike Chain ◽  
C Terminus

The poly-immunoglobulin domain region of titin, located within the elastic section of this giant muscle protein, determines the extensibility of relaxed myofibrils mainly at shorter physiological lengths. To elucidate this region's contribution to titin elasticity, we measured the elastic properties of the N-terminal I-band Ig region by using immunofluorescence/immunoelectron microscopy and myofibril mechanics and tried to simulate the results with a model of entropic polymer elasticity. Rat psoas myofibrils were stained with titin-specific antibodies flanking the Ig region at the N terminus and C terminus, respectively, to record the extension behaviour of that titin segment. The segment's end-to-end length increased mainly at small stretch, reaching approximately 90% of the native contour length of the Ig region at a sarcomere length of 2.8 microm. At this extension, the average force per single titin molecule, deduced from the steady-state passive length-tension relation of myofibrils, was approximately 5 or 2.5 pN, depending on whether we assumed a number of 3 or 6 titins per half thick filament. When the force-extension curve constructed for the Ig region was simulated by the wormlike chain model, best fits were obtained for a persistence length, a measure of the chain's bending rigidity, of 21 or 42 nm (for 3 or 6 titins/half thick filament), which correctly reproduced the curve for sarcomere lengths up to 3.4 microm. Systematic deviations between data and fits above that length indicated that forces of >30 pN per titin strand may induce unfolding of Ig modules. We conclude that stretches of at least 5–6 Ig domains, perhaps coinciding with known super repeat patterns of these titin modules in the I-band, may represent the unitary lengths of the wormlike chain. The poly-Ig regions might thus act as compliant entropic springs that determine the minute levels of passive tension at low extensions of a muscle fiber.

scholarly journals Sugar-Pucker Force-Induced Transition in Single-Stranded DNA

2021 ◽  
Vol 22 (9) ◽  
pp. 4745
Author(s):  
Xavier Viader-Godoy ◽  
Maria Manosas ◽  
Felix Ritort
Keyword(s):  
Optical Tweezers ◽  
Conformational Transition ◽  
Persistence Length ◽  
Elastic Response ◽  
Contour Length ◽  
Dna Unwinding ◽  
Chain Model ◽  
Force Extension ◽  
Single Stranded Dna ◽  
Sugar Pucker

The accurate knowledge of the elastic properties of single-stranded DNA (ssDNA) is key to characterize the thermodynamics of molecular reactions that are studied by force spectroscopy methods where DNA is mechanically unfolded. Examples range from DNA hybridization, DNA ligand binding, DNA unwinding by helicases, etc. To date, ssDNA elasticity has been studied with different methods in molecules of varying sequence and contour length. A dispersion of results has been reported and the value of the persistence length has been found to be larger for shorter ssDNA molecules. We carried out pulling experiments with optical tweezers to characterize the elastic response of ssDNA over three orders of magnitude in length (60–14 k bases). By fitting the force-extension curves (FECs) to the Worm-Like Chain model we confirmed the above trend:the persistence length nearly doubles for the shortest molecule (60 b) with respect to the longest one (14 kb). We demonstrate that the observed trend is due to the different force regimes fitted for long and short molecules, which translates into two distinct elastic regimes at low and high forces. We interpret this behavior in terms of a force-induced sugar pucker conformational transition (C3′-endo to C2′-endo) upon pulling ssDNA.

FINITE ELEMENT MODELING OF THE THERMAL FLUCTUATIONS OF A SINGLE ANISOTROPIC POLYMER

2013 ◽  
Vol 13 (04) ◽  
pp. 1350056
Author(s):  
SANDER L. POELERT ◽  
HARRIE H. WEINANS ◽  
AMIR A. ZADPOOR
Keyword(s):  
Finite Element ◽  
Experimental Work ◽  
Numerical Models ◽  
Persistence Length ◽  
Mean Square Displacement ◽  
Transversely Isotropic ◽  
Thermal Fluctuations ◽  
Contour Length ◽  
Chain Model ◽  
Thermal Dynamics

Thermal fluctuations of microtubules (MTs) and other cytoskeletal filaments govern to a great extent the complex rheological properties of the cytoskeleton in eukaryotic cells. In recent years, much effort has been put into capturing the dynamics of these fluctuations by means of analytical and numerical models. These attempts have been very successful for, but also remain limited to, isotropic polymers. To correctly interpret experimental work on (strongly) anisotropic semiflexible polymers, there is a need for a numerical modeling tool that accurately captures the dynamics of polymers with anisotropic material properties. In the current study, we present a finite element (FE) framework for simulating the thermal dynamics of a single anisotropic semiflexible polymer. First, we demonstrated the accuracy of our framework by comparison of the simulated mean square displacement (MSD) of the end-to-end distance with analytical predictions based on the worm-like chain model. Then, we implemented a transversely isotropic material model, characteristic for biopolymers such as MTs, and studied the persistence length for various ratios between the longitudinal shear modulus, G12, and corresponding Young's modulus, E1. Finally, we put our findings in context by addressing a recent experimental work on grafted transversely isotropic MTs. In that research, a simplified static mechanical model was used to deduce a very high level of MT anisotropy to explain the observation that the persistence length of grafted MTs increases as contour length increases. We showed, by means of our FE framework, that the anisotropic properties cannot account for the reported length-dependent persistence length.

scholarly journals Semiflexible Polymers Interacting with Planar Surfaces: Weak versus Strong Adsorption

Polymers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 255 ◽  
Author(s):  
Andrey Milchev ◽  
Kurt Binder
Keyword(s):  
Orientational Order ◽  
Persistence Length ◽  
Distribution Functions ◽  
Coarse Grained ◽  
Gyration Radius ◽  
Contour Length ◽  
Local Order ◽  
Chain Model ◽  
Semiflexible Polymers ◽  
Wide Range

Semiflexible polymers bound to planar substrates by a short-range surface potential are studied by Molecular Dynamics simulations to clarify the extent to which these chain molecules can be considered as strictly two-dimensional. Applying a coarse-grained bead-spring model, the chain length N and stiffness κ as well as the strength of the adsorption potential ϵ w a l l are varied over a wide range. The excluded-volume (EV) interactions inherent in this model can also be “switched off” to provide a discretized version of the Kratky–Porod wormlike chain model. We study both local order parameters (fraction f of monomers within the range of the potential, bond-orientational order parameter η ) and the mean square gyration radius parallel, ⟨ R g 2 ⟩ | | , and perpendicular, ⟨ R g 2 ⟩ ⊥ , to the wall. While for strongly adsorbed chains EV has negligible effect on f and η , we find that ⟨ R g 2 ⟩ | | is strongly affected when the chain contour length exceeds the persistence length. Monomer coordinates in perpendicular (⊥) direction are correlated over the scale of the deflection length which is estimated. It is found that f , η , and ⟨ R g 2 ⟩ ⊥ converge to their asymptotic values with 1 / N corrections. For both weakly and strongly adsorbed chains, the distribution functions of “loops”, “trains”, and “tails” are analyzed. Some consequences pertaining to the analysis of experiments on adsorbed semiflexible polymers are pointed out.

scholarly journals Submicrometer elasticity of double-stranded DNA revealed by precision force-extension measurements with magnetic tweezers

2019 ◽  
Vol 5 (6) ◽  
pp. eaav1697 ◽  
Author(s):  
Min Ju Shon ◽  
Sang-Hyun Rah ◽  
Tae-Young Yoon
Keyword(s):  
Single Molecule ◽  
Persistence Length ◽  
Gc Content ◽  
Magnetic Tweezers ◽  
Force Variability ◽  
Chain Model ◽  
Force Extension ◽  
Dna Hairpins ◽  
Double Stranded Dna ◽  
Order Of Magnitude

Submicrometer elasticity of double-stranded DNA (dsDNA) governs nanoscale bending of DNA segments and their interactions with proteins. Single-molecule force spectroscopy, including magnetic tweezers (MTs), is an important tool for studying DNA mechanics. However, its application to short DNAs under 1 μm is limited. We developed an MT-based method for precise force-extension measurements in the 100-nm regime that enables in situ correction of the error in DNA extension measurement, and normalizes the force variability across beads by exploiting DNA hairpins. The method reduces the lower limit of tractable dsDNA length down to 198 base pairs (bp) (67 nm), an order-of-magnitude improvement compared to conventional tweezing experiments. Applying this method and the finite worm-like chain model we observed an essentially constant persistence length across the chain lengths studied (198 bp to 10 kbp), which steeply depended on GC content and methylation. This finding suggests a potential sequence-dependent mechanism for short-DNA elasticity.

A functional knock-out of titin results in defective myofibril assembly

2000 ◽  
Vol 113 (8) ◽  
pp. 1405-1414 ◽  
Author(s):  
P.F. van der Ven ◽  
J.W. Bartsch ◽  
M. Gautel ◽  
H. Jockusch ◽  
D.O. Furst
Keyword(s):  
Cell Line ◽  
Muscle Protein ◽  
Mutant Cell ◽  
Thick Filament ◽  
Homozygous Deletion ◽  
Sarcomeric Proteins ◽  
Filament Formation ◽  
Western Blots ◽  
Knock Out ◽  
Molecular Ruler

Titin, also called connectin, is a giant muscle protein that spans the distance from the sarcomeric Z-disc to the M-band. Titin is thought to direct the assembly of sarcomeres and to maintain sarcomeric integrity by interacting with numerous sarcomeric proteins and providing a mechanical linkage. Since severe defects of such an important molecule are likely to result in embryonic lethality, a cell culture model should offer the best practicable tool to probe the cellular functions of titin. The myofibroblast cell line BHK-21/C13 was described to assemble myofibrils in culture. We have now characterized the sub-line BHK-21-Bi, which bears a small deletion within the titin gene. RNA analysis revealed that in this mutant cell line only a small internal portion of the titin mRNA is deleted. However, western blots, immunofluorescence microscopy and immunoprecipitation experiments showed that only the N-terminal, approx. 100 kDa central Z-disc portion of the 3 MDa titin protein is expressed, due to the homozygous deletion in the gene. Most importantly, in BHK-21-Bi cells the formation of thick myosin filaments and the assembly of myofibrils are impaired, although sarcomeric proteins are expressed. Lack of thick filament formation and of ordered actin-myosin arrays was confirmed by electron microscopy. Myogenisation induced by transfection with MyoD yielded myofibrils only in myotubes formed from wild type and not from mutant cells, ruling out that a principal failure in myogenic commitment of the BHK-21-Bi cells might cause the observed effects. These experiments provide the first direct evidence for the crucial role of titin in both thick filament formation as a molecular ruler and in the coordination of myofibrillogenesis.

scholarly journals Sequence-dependent Three Interaction Site (TIS) Model for Single and Double-stranded DNA

2018 ◽  
Author(s):  
Debayan Chakraborty ◽  
Naoto Hori ◽  
D. Thirumalai
Keyword(s):  
Electrostatic Interactions ◽  
Persistence Length ◽  
Data Bank ◽  
Coarse Grained ◽  
Force Extension ◽  
Sequence Dependence ◽  
Coarse Grained Model ◽  
Interaction Sites ◽  
Double Stranded Dna ◽  
Centers Of Mass

AbstractWe develop a robust coarse-grained model for single and double stranded DNA by representing each nucleotide by three interaction sites (TIS) located at the centers of mass of sugar, phosphate, and base. The resulting TIS model includes base-stacking, hydrogen bond, and electrostatic interactions as well as bond-stretching and bond angle potentials that account for the polymeric nature of DNA. The choices of force constants for stretching and the bending potentials were guided by a Boltzmann inversion procedure using a large representative set of DNA structures extracted from the Protein Data Bank. Some of the parameters in the stacking interactions were calculated using a learning procedure, which ensured that the experimentally measured melting temperatures of dimers are faithfully reproduced. Without any further adjustments, the calculations based on the TIS model reproduces the experimentally measured salt and sequence dependence of the size of single stranded DNA (ssDNA), as well as the persistence lengths of poly(dA) and poly(dT) chains. Interestingly, upon application of mechanical force the extension of poly(dA) exhibits a plateau, which we trace to the formation of stacked helical domains. In contrast, the force-extension curve (FEC) of poly(dT) is entropic in origin, and could be described by a standard polymer model. We also show that the persistence length of double stranded DNA, formed from two complementary ssDNAs with one hundred and thirty base pairs, is consistent with the prediction based on the worm-like chain. The persistence length, which decreases with increasing salt concentration, is in accord with the Odijk-Skolnick-Fixman theory intended for stiff polyelectrolyte chains near the rod limit. The range of applications, which did not require adjusting any parameter after the initial construction based solely on PDB structures and melting profiles of dimers, attests to the transferability and robustness of the TIS model for ssDNA and dsDNA.

scholarly journals Mechanical Response of Carbon Nanotube Bundle to Lateral Compression

Computation ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 27 ◽  
Author(s):  
Dina U. Abdullina ◽  
Elena A. Korznikova ◽  
Volodymyr I. Dubinko ◽  
Denis V. Laptev ◽  
Alexey A. Kudreyko ◽  
...  
Keyword(s):  
Phase Transition ◽  
Carbon Nanotube ◽  
Order Phase Transition ◽  
Mechanical Response ◽  
Van Der Waals ◽  
Van Der Waals Interactions ◽  
Structure Evolution ◽  
Biaxial Compression ◽  
Chain Model ◽  
Bending Rigidity

Structure evolution and mechanical response of the carbon nanotube (CNT) bundle under lateral biaxial compression is investigated in plane strain conditions using the chain model. In this model, tensile and bending rigidity of CTN walls, and the van der Waals interactions between them are taken into account. Initially the bundle in cross section is a triangular lattice of circular zigzag CNTs. Under increasing strain control compression, several structure transformations are observed. Firstly, the second-order phase transition leads to the crystalline structure with doubled translational cell. Then the first-order phase transition takes place with the appearance of collapsed CNTs. Further compression results in increase of the fraction of collapsed CNTs at nearly constant compressive stress and eventually all CNTs collapse. It is found that the potential energy of the CNT bundle during deformation changes mainly due to bending of CNT walls, while the contribution from the walls tension-compression and from the van der Waals energies is considerably smaller.

Orthotropic Hyperelasticity in Terms of an Arbitrary Molecular Chain Model

2001 ◽  
Vol 69 (2) ◽  
pp. 198-201 ◽  
Author(s):  
J. E. Bischoff ◽  
E. M. Arruda ◽  
K. Grosh
Keyword(s):  
Constitutive Model ◽  
Strain Energy Function ◽  
Constitutive Law ◽  
Orthotropic Materials ◽  
Chain Model ◽  
Wormlike Chain ◽  
General Terms ◽  
Mechanical Models ◽  
Orthotropic Hyperelasticity ◽  
Wormlike Chain Model

There are many statistical mechanical models of long-chain models, two of which are the freely jointed chain model and the wormlike chain model. A continuum constitutive law for hyperelastic orthotropic materials has recently been developed using the freely jointed chain model as its basis. In this note, the continuum strain energy function is recast in general terms allowing for the incorporation of an arbitrary macromolecular constitutive model. In particular, the orthotropic constitutive model is recast using the wormlike chain model in place of the freely jointed chain model and the effects of this alternation are examined.

Influence of Nanochannel Inlet Structure Upon DNA Capture Ratio

2011 ◽  
Author(s):  
Jiahao Wu ◽  
Hong Wang ◽  
Jinsoo Kim ◽  
Freddy Murphy ◽  
Steven A. Soper ◽  
...  
Keyword(s):  
Real Time ◽  
Persistence Length ◽  
Contour Length ◽  
Dna Molecules ◽  
Channel Diameter ◽  
Dna Molecule ◽  
Capture Ratio ◽  
Sequence Variations ◽  
Dna Capture ◽  
Dna Chain

DNA molecule will be stretched to its near full contour length inside a nanochannel when the channel diameter is less than the DNA persistence length.1–3 It provides the possibility of real time lab-free-analysis of analysis, such as screening of sequence variations of DNA molecules.3 The key process for this nanochannel-based analysis is to drive DNA molecule electrophoretically through the nanochannel and read out the information of the DNA chain while it is passing the channel.2, 3

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