scholarly journals Compression stiffening of fibrous networks with stiff inclusions

2020 ◽  
Vol 117 (35) ◽  
pp. 21037-21044
Author(s):  
Jordan L. Shivers ◽  
Jingchen Feng ◽  
Anne S. G. van Oosten ◽  
Herbert Levine ◽  
Paul A. Janmey ◽  
...  
Keyword(s):  
Phase Diagram ◽  
Qualitative Agreement ◽  
Three Dimensional ◽  
Quantitative Agreement ◽  
Coarse Grained ◽  
Fiber Network ◽  
Coarse Grained Model ◽  
Fibrous Network ◽  
Stress Propagation ◽  
Stiffening Effect

Tissues commonly consist of cells embedded within a fibrous biopolymer network. Whereas cell-free reconstituted biopolymer networks typically soften under applied uniaxial compression, various tissues, including liver, brain, and fat, have been observed to instead stiffen when compressed. The mechanism for this compression-stiffening effect is not yet clear. Here, we demonstrate that when a material composed of stiff inclusions embedded in a fibrous network is compressed, heterogeneous rearrangement of the inclusions can induce tension within the interstitial network, leading to a macroscopic crossover from an initial bending-dominated softening regime to a stretching-dominated stiffening regime, which occurs before and independently of jamming of the inclusions. Using a coarse-grained particle-network model, we first establish a phase diagram for compression-driven, stretching-dominated stress propagation and jamming in uniaxially compressed two- and three-dimensional systems. Then, we demonstrate that a more detailed computational model of stiff inclusions in a subisostatic semiflexible fiber network exhibits quantitative agreement with the predictions of our coarse-grained model as well as qualitative agreement with experiments.

Riboswitch Folds to Holo-Form Like Structure Even in the Absence of Cognate Ligand at High Mg2+ Concentration

2021 ◽  
Author(s):  
Sunil Kumar ◽  
Govardhan Reddy
Keyword(s):  
Specific Binding ◽  
Three Dimensional ◽  
Coarse Grained ◽  
Thiamine Pyrophosphate ◽  
Initial Increase ◽  
Free Energy Surface ◽  
Physiological Concentration ◽  
Coarse Grained Model ◽  
Non Coding Rna ◽  
Thermodynamic Conditions

Riboswitches are non-coding RNA that regulate gene expression by folding into specific three-dimensional structures (holo-form) upon binding by their cognate ligand in the presence of Mg2+. Riboswitch functioning is also hypothesized to be under kinetic control requiring large cognate ligand concentrations. We ask the question under thermodynamic conditions, can the riboswitches populate holo-form like structures in the absence of their cognate ligands only in the presence of Mg2+. We addressed this question using thiamine pyrophosphate (TPP) riboswitch as a model system and computer simulations using a coarse-grained model for RNA. The folding free energy surface (FES) shows that with the initial increase in Mg2+ concentration ([Mg2+]), TPP AD undergoes a barrierless collapse in its dimensions. On further increase in [Mg2+], intermediates separated by barriers appear on the FES, and one of the intermediates has a TPP ligand-binding competent structure. We show that site-specific binding of the Mg2+ aids in the formation of tertiary contacts. For [Mg2+] greater than physiological concentration, AD folds into its holo-form like structure even in the absence of the TPP ligand. The folding kinetics shows that it populates an intermediate due to the misalignment of the two arms in the TPP AD, which acts as a kinetic trap leading to larger folding timescales. The predictions of the intermediate structures from the simulations are amenable for experimental verification.

Symmetry-adapted digital modeling III. Coarse-grained icosahedral viruses

2016 ◽  
Vol 72 (3) ◽  
pp. 324-337 ◽  
Author(s):  
A. Janner
Keyword(s):  
Lattice Point ◽  
Three Dimensional ◽  
Structural Data ◽  
Data Bank ◽  
Coarse Grained ◽  
Large Set ◽  
Fine Grained ◽  
Coarse Grained Model ◽  
Digital Modeling ◽  
Icosahedral Viruses

Considered is the coarse-grained modeling of icosahedral viruses in terms of a three-dimensional lattice (the digital modeling lattice) selected among the projected points in space of a six-dimensional icosahedral lattice. Backbone atomic positions (Cα's for the residues of the capsid and phosphorus atoms P for the genome nucleotides) are then indexed by their nearest lattice point. This leads to a fine-grained lattice point characterization of the full viral chains in the backbone approximation (denoted as digital modeling). Coarse-grained models then follow by a proper selection of the indexed backbone positions, where for each chain one can choose the desired coarseness. This approach is applied to three viruses, the Satellite tobacco mosaic virus, the bacteriophage MS2 and the Pariacoto virus, on the basis of structural data from the Brookhaven Protein Data Bank. In each case the various stages of the procedure are illustrated for a given coarse-grained model and the corresponding indexed positions are listed. Alternative coarse-grained models have been derived and compared. Comments on related results and approaches, found among the very large set of publications in this field, conclude this article.

scholarly journals An Accurate Estimate of the Free Energy and Phase Diagram of All-DNA Bulk Fluids

2018 ◽  
Author(s):  
Emanuele Locatelli ◽  
Lorenzo Rovigatti
Keyword(s):  
Phase Diagram ◽  
Free Energy ◽  
Large Scale ◽  
Nearest Neighbor ◽  
Numerical Study ◽  
Thermodynamic Description ◽  
Numerical Approach ◽  
Quantitative Agreement ◽  
State Theory ◽  
Coarse Grained

We present a numerical study in which large-scale bulk simulations of self-assembled DNA constructs have been carried out with a realistic coarse-grained model. The investigation aims at obtaining a precise, albeit numerically demanding, estimate of the free energy for such systems. We then, in turn, use these accurate results to validate a recently proposed theoretical approach that builds on a liquid-state theory, the Wertheim theory, to compute the phase diagram of all-DNA fluids. This hybrid theoretical/numerical approach, based on the lowest order virial expansion and a nearest-neighbor DNA model, can provide, in an undemanding way, a thermodynamic description of DNA associating fluids that is in semi-quantitative agreement with experiments. We show that the predictions of such scheme are as accurate as the ones obtained with more sophisticated methods. We also demonstrate the flexibility of the approach by incorporating non-trivial additional contributions that go beyond the nearest-neighbor model to compute the DNA hybridization free energy.

scholarly journals The Effect of Enzymatic Crosslink Degradation on the Mechanics of the Anterior Cruciate Ligament: A Hybrid Multi-Domain Model

2021 ◽  
Vol 11 (18) ◽  
pp. 8580
Author(s):  
Fadi Al Khatib ◽  
Afif Gouissem ◽  
Armin Eilaghi ◽  
Malek Adouni
Keyword(s):  
Cruciate Ligament ◽  
Three Dimensional ◽  
Domain Model ◽  
Coarse Grained ◽  
Elastic Response ◽  
Type I ◽  
Coarse Grained Model ◽  
Promising Tool ◽  
Collagen Molecules ◽  
Anterior Cruciate

The anterior cruciate ligament’s (ACL) mechanics is an important factor governing the ligament’s integrity and, hence, the knee joint’s response. Despite many investigations in this area, the cause and effect of injuries remain unclear or unknown. This may be due to the complexity of the direct link between macro- and micro-scale damage mechanisms. In the first part of this investigation, a three-dimensional coarse-grained model of collagen fibril (type I) was developed using a bottom-up approach to investigate deformation mechanisms under tensile testing. The output of this molecular level was used later to calibrate the parameters of a hierarchical multi-scale fibril-reinforced hyper-elastoplastic model of the ACL. Our model enabled us to determine the mechanical behavior of the ACL as a function of the basic response of the collagen molecules. Modeled elastic response and damage distribution were in good agreement with the reported measurements and computational investigations. Our results suggest that degradation of crosslink content dictates the loss of the stiffness of the fibrils and, hence, damage to the ACL. Therefore, the proposed computational frame is a promising tool that will allow new insights into the biomechanics of the ACL.

scholarly journals Kinematics of the lever arm swing in myosin VI

2017 ◽  
Vol 114 (22) ◽  
pp. E4389-E4398 ◽  
Author(s):  
Mauro L. Mugnai ◽  
D. Thirumalai
Keyword(s):  
Rotational Diffusion ◽  
Quantitative Agreement ◽  
Motor Domain ◽  
Coarse Grained ◽  
Power Stroke ◽  
Myosin Vi ◽  
Step Size ◽  
Arm Swing ◽  
Coarse Grained Model ◽  
Lever Arm

Myosin VI (MVI) is the only known member of the myosin superfamily that, upon dimerization, walks processively toward the pointed end of the actin filament. The leading head of the dimer directs the trailing head forward with a power stroke, a conformational change of the motor domain exaggerated by the lever arm. Using a unique coarse-grained model for the power stroke of a single MVI, we provide the molecular basis for its motility. We show that the power stroke occurs in two major steps. First, the motor domain attains the poststroke conformation without directing the lever arm forward; and second, the lever arm reaches the poststroke orientation by undergoing a rotational diffusion. From the analysis of the trajectories, we discover that the potential that directs the rotating lever arm toward the poststroke conformation is almost flat, implying that the lever arm rotation is mostly uncoupled from the motor domain. Because a backward load comparable to the largest interhead tension in a MVI dimer prevents the rotation of the lever arm, our model suggests that the leading-head lever arm of a MVI dimer is uncoupled, in accord with the inference drawn from polarized total internal reflection fluorescence (polTIRF) experiments. Without any adjustable parameter, our simulations lead to quantitative agreement with polTIRF experiments, which validates the structural insights. Finally, in addition to making testable predictions, we also discuss the implications of our model in explaining the broad step-size distribution of the MVI stepping pattern.

scholarly journals A coarse-grained approach to model the dynamics of the actomyosin cortex

2021 ◽  
Author(s):  
Miguel Hernandez-del-valle ◽  
Andrea Valencia-Exposito ◽  
Antonio Lopez-Izquierdo ◽  
pau casanova ferrer ◽  
Pedro Tarazona ◽  
...  
Keyword(s):  
Network Formation ◽  
Three Dimensional ◽  
Coarse Grained ◽  
Cell Cortex ◽  
Biological Processes ◽  
Coarse Grained Model ◽  
Long Time ◽  
Mesoscopic Level ◽  
Myosin Motors

The dynamics of the actomyosin machinery is at the core of many important biological processes. Several relevant cellular responses such as the rhythmic compression of the cell cortex are governed, at a mesoscopic level, by the nonlinear interaction between actin monomers, actin crosslinkers and myosin motors. Coarse grained models are an optimal tool to study actomyosin systems, since they can include processes that occur at long time and space scales, while maintaining the most relevant features of the molecular interactions. Here, we present a coarse grained model of a two-dimensional actomyosin cortex, adjacent to a three-dimensional cytoplasm. Our simplified model incorporates only well characterized interactions between actin monomers, actin cross- linkers and myosin, and it is able to reproduce many of the most important aspects of actin filament and actomyosin network formation, such as dynamics of polymerization and depolymerization, treadmilling, network formation and the autonomous oscilla- tory dynamics of actomyosin. Furthermore, the model can be used to predict the in vivo response of actomyosin networks to changes in key parameters of the system, such as alterations in the anchor of actin filaments to the cell cortex.

scholarly journals On the Importance of Hydrodynamic Interactions in the Stepping Kinetics of Kinesin

2016 ◽  
Author(s):  
Dave Thirumalai ◽  
Yonathan Goldtzvik ◽  
Zhechun Zhang
Keyword(s):  
Coiled Coil ◽  
Quantitative Agreement ◽  
Single Step ◽  
Hydrodynamic Interactions ◽  
Coarse Grained ◽  
Coarse Grained Model ◽  
Target Binding ◽  
Conventional Kinesin ◽  
Kinetics Of ◽  
Target Binding Site

Conventional kinesin walks by a hand-over-hand mechanism on the microtubule (MT) by taking ∼ 8nmdiscrete steps, and consumes one ATP molecule per step. The time needed to complete a single step is on the order of twenty microseconds. We show, using simulations of a coarse-grained model of the complex containing the two motor heads, the MT, and the coiled coil that in order to obtain quantitative agreement with experiments for the stepping kinetics hydrodynamic interactions (HI) have to be included. In simulations without hydrodynamic interactions spanning nearly twenty microseconds not a single step was completed in hundred trajectories. In sharp contrast, nearly 14% of the steps reached the target binding site within 6 microseconds when HI were included. Somewhat surprisingly, there are qualitative differences in the diffusion pathways in simulations with and without HI. The extent of movement of the trailing head of kinesin on the MT during the diffusion stage of stepping is considerably greater in simulations with HI than in those without HI. Our results suggest that inclusion of HI is crucial in the accurate description of motility of other motors as well.

scholarly journals Coarse-Grained Model for Simulation of RNA Three-Dimensional Structures

2010 ◽  
Vol 114 (42) ◽  
pp. 13497-13506 ◽  
Author(s):  
Zhen Xia ◽  
David Paul Gardner ◽  
Robin R. Gutell ◽  
Pengyu Ren
Keyword(s):  
Three Dimensional ◽  
Coarse Grained ◽  
Coarse Grained Model

scholarly journals Modeling structure, stability and flexibility of double-stranded RNAs in salt solutions

2018 ◽  
Author(s):  
L. Jin ◽  
Y.Z. Shi ◽  
C.J. Feng ◽  
Y.L. Tan ◽  
Z.J. Tan
Keyword(s):  
Electrostatic Potential ◽  
Cell Metabolism ◽  
3D Structure ◽  
Three Dimensional ◽  
Coarse Grained ◽  
Structure Stability ◽  
Salt Solutions ◽  
3D Structures ◽  
Coarse Grained Model ◽  
Wide Range

AbstractDouble-stranded (ds) RNAs play essential roles in many processes of cell metabolism. The knowledge of three-dimensional (3D) structure, stability and flexibility of dsRNAs in salt solutions is important for understanding their biological functions. In this work, we further developed our previously proposed coarse-grained model to predict 3D structure, stability and flexibility for dsRNAs in monovalent and divalent ion solutions through involving an implicit structure-based electrostatic potential. The model can make reliable predictions for 3D structures of extensive dsRNAs with/without bulge/internal loops from their sequences, and the involvement of the structure-based electrostatic potential and corresponding ion condition can improve the predictions on 3D structures of dsRNAs in ion solutions. Furthermore, the model can make good predictions on thermal stability for extensive dsRNAs over the wide range of monovalent/divalent ion concentrations, and our analyses show that thermally unfolding pathway of a dsRNA is generally dependent on its length as well as its sequence. In addition, the model was employed to examine the salt-dependent flexibility of a dsRNA helix and the calculated salt-dependent persistence lengths are in good accordance with experiments.

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