scholarly journals Coarse-grained simulations of actomyosin rings point to a nodeless model involving both unipolar and bipolar myosins

2018 ◽  
Vol 29 (11) ◽  
pp. 1318-1331 ◽  
Author(s):  
Lam T. Nguyen ◽  
Matthew T. Swulius ◽  
Samya Aich ◽  
Mithilesh Mishra ◽  
Grant J. Jensen
Keyword(s):  
Cell Wall ◽  
Actin Filaments ◽  
Three Dimensional ◽  
Coarse Grained ◽  
Eukaryotic Cells ◽  
Ring Assembly ◽  
Assembly Result ◽  
Microscope Images ◽  
Coarse Grained Simulations ◽  
Electron Cryotomography

Cytokinesis in many eukaryotic cells is orchestrated by a contractile actomyosin ring. While many of the proteins involved are known, the mechanism of constriction remains unclear. Informed by the existing literature and new three-dimensional (3D) molecular details from electron cryotomography, here we develop 3D coarse-grained models of actin filaments, unipolar and bipolar myosins, actin cross-linkers, and membranes and simulate their interactions. Assuming that local force on the membrane results in inward growth of the cell wall, we explored a matrix of possible actomyosin configurations and found that node-based architectures like those presently described for ring assembly result in membrane puckers not seen in electron microscope images of real cells. Instead, the model that best matches data from fluorescence microscopy, electron cryotomography, and biochemical experiments is one in which actin filaments transmit force to the membrane through evenly distributed, membrane-attached, unipolar myosins, with bipolar myosins in the ring driving contraction. While at this point this model is only favored (not proven), the work highlights the power of coarse-grained biophysical simulations to compare complex mechanistic hypotheses.

scholarly journals Coarse-grained simulations of actomyosin rings point to a nodeless model involving both unipolar and bipolar myosins

2017 ◽  
Author(s):  
Lam T. Nguyen ◽  
Matthew T. Swulius ◽  
Samya Aich ◽  
Mithilesh Mishra ◽  
Grant J. Jensen
Keyword(s):  
Experimental Data ◽  
Cell Division ◽  
Fluorescence Microscopy ◽  
Actin Filaments ◽  
Coarse Grained ◽  
Eukaryotic Cells ◽  
Ring Assembly ◽  
Assembly Result ◽  
Coarse Grained Simulations ◽  
Electron Cryotomography

AbstractCytokinesis in most eukaryotic cells is orchestrated by a contractile actomyosin ring. While many of the proteins involved are known, the mechanism of constriction remains unclear. Informed by existing literature and new 3D molecular details from electron cryotomography, here we develop 3D coarse-grained models of actin filaments, unipolar and bipolar myosins, actin crosslinkers, and membranes and simulate their nteractions. Exploring a matrix of possible actomyosin configurations suggested that node-based architectures ike those presently described for ring assembly result in membrane puckers not seen in EM images of real cells. Instead, the model that best matches data from fluorescence microscopy, electron cryotomography, and biochemical experiments is one in which actin filaments transmit force to the membrane through evenly-distributed, membrane-attached, unipolar myosins, with bipolar myosins in the ring driving contraction. While at this point this model is only favored (not proven), the work highlights the power of coarse-grained biophysical simulations to compare complex mechanistic hypotheses.Significance StatementIn most eukaryotes, a ring of actin and myosin drives cell division, but how the elements of the ring are arranged and constrict remain unclear. Here we use 3D coarse-grained simulations to explore various possibilities. Our simulations suggest that if actomyosin is arranged in nodes (as suggested by a popular model of ring assembly), the membrane distorts in ways not seen experimentally. Instead, actin and myosin are more ikely uniformly distributed around the ring. In the model that best fits experimental data, ring tension is generated by interactions between bipolar myosins and actin, and transmitted to the membrane via unipolar myosins. Technologically the study highlights how coarse-grained simulations can test specific mechanistic hypotheses by comparing their predicted outcomes to experimental results.

Molecular Modeling Computer Simulations of Organic Polymers: A Novel Computer Simulation Technique to Characterize Nanostructured Materials

2003 ◽  
Vol 788 ◽  
Author(s):  
Sarah G. Schulz ◽  
Hubert Kuhn ◽  
Günter Schmid
Keyword(s):  
Computer Simulations ◽  
Dissipative Particle Dynamics ◽  
Three Dimensional ◽  
Colloidal Suspensions ◽  
Simulation Technique ◽  
Coarse Grained ◽  
Organic Polymer ◽  
Random Forces ◽  
Coarse Grained Simulations ◽  
Immiscible Mixtures

ABSTRACTThe understanding and prediction of complex nanostructured self-assemblies such as colloidal suspensions, micelles, immiscible mixtures, microemulsions, etc., represent a challenge for conventional methods of simulation due to the presence of different time scales in their dynamics.We have recently successfully applied a novel computer simulations technique, Dissipative Particle Dynamics (DPD), to model the behavior of diblockcopolymers at the water/oil interface. With the use of a simple model we have performed simulations of polymer/water/oil systems at different concentrations.We present the results of nanoscale “coarse-grained” simulations with DPD. DPD is a mesoscale simulation technique that has been introduced in order to simulate three-dimensional structures of organic polymer aggregates.In DPD the polymer is modeled using particles which are interacting by conservative, dissipative and random forces. Particles are not regarded as molecules but rather as droplets or nanoclusters of molecules.We have successfully applied this technique to simulate the three-dimensional structures of microemulsions, e.g. the bicontinuous phase of a surfactant in water and oil, in domains of less than 100 nm. The different structures of the polymer/water/oil system were effectively characterized with DPD and are in remarkable agreement with the experiment.The DPD method proofed to be a reliable tool to get a better understanding of the nanostructure of self-assemblies and is therefore applicable to support the often complicated experiments or even to obtain experimentally unavai1able data.

scholarly journals Modeling myosin Va liposome transport through actin filament networks reveals a percolation threshold that modulates transport properties

2021 ◽  
Author(s):  
Sam Walcott ◽  
David M Warshaw
Keyword(s):  
Phase Transition ◽  
Actin Filament ◽  
Actin Filaments ◽  
Three Dimensional ◽  
Fold Increase ◽  
Coarse Grained ◽  
Actin Network ◽  
Cargo Delivery ◽  
Myosin Va ◽  
Filament Networks

Myosin Va (myoVa) motors transport membrane-bound cargo through three-dimensional, intracellular actin filament networks. We developed a coarse-grained, in silico model to predict how actin filament density (3-800 filaments) within a randomly oriented actin network affects fluid-like liposome (350nm vs. 1,750nm) transport by myoVa motors. 5,000 simulated liposomes transported within each network adopted one of three states: transport, tug of war, or diffusion. Diffusion due to liposome detachment from actin rarely occurred given at least 10 motors on the liposome surface. However, with increased actin density, liposomes transitioned from primarily directed transport on single actin filaments to an apparent random walk, resulting from a mixture of transport and tug of wars as the probability of encountering additional actin filaments increased. This phase transition arises from a percolation phase transition at a critical number of accessible actin filaments, Nc. Nc, is a geometric property of the actin network that depends only on the position and polarity of the actin filaments and the liposome diameter, as evidenced by a five-fold increase in liposome diameter resulting in a five-fold decrease in Nc. Thus, in cells, actin network density and cargo size may be regulated to match cargo delivery to the cell's physiological demands.

Cell Cytoskeleton

2015 ◽  
Author(s):  
Matthieu Piel ◽  
Raphael Voituriez
Keyword(s):  
Cell Wall ◽  
Cell Polarity ◽  
Molecular Motors ◽  
Actin Filaments ◽  
Soft Matter ◽  
Coarse Grained ◽  
Cellular Functions ◽  
Cell Cytoskeleton ◽  
Matter Model ◽  
Soft Matter Physics

This article examines the ‘active’ part of the cell cytoskeleton — which mostly corresponds to actin and tubulin polymers and associated molecular motors — using theoretical tools derived from a soft matter physics coarse-grained approach. It begins with an overview of the cytoskeleton and its components, which include actin filaments and gels, microtubules and specialized microtubule-based organelles, molecular motors, intermediate filaments, the plasma membrane and glycocalix, the cell wall, and the extracellular matrix. It then describes coarse-grained models of the cytoskeleton and gives two examples of models for important cellular functions, namely cell migration and cell polarity. It also proposes a new kind of soft matter model providing a coarse-grained description of cytoskeletal polymers and associated molecular motors.

scholarly journals Structure of the fission yeast actomyosin ring during constriction

2017 ◽  
Author(s):  
Matthew T. Swulius ◽  
Lam T. Nguyen ◽  
Mark S. Ladinsky ◽  
Davi R. Ortega ◽  
Samya Aich ◽  
...  
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Actin Filaments ◽  
Focused Ion Beam ◽  
Nearest Neighbor ◽  
Ion Beam ◽  
Three Dimensional ◽  
Model Organism ◽  
Leading Edge ◽  
Specimen Preparation ◽  
Electron Cryotomography

AbstractCell division in many eukaryotes is driven by a ring containing actin and myosin. While much is known about the main proteins involved, the precise arrangement of actin filaments within the contractile machinery, and how force is transmitted to the membrane remains unclear. Here we use cryosectioning and cryo-focused ion beam milling to gain access to cryo-preserved actomyosin rings in Schizosaccharomyces pombe for direct three-dimensional imaging by electron cryotomography. Our results show that straight, overlapping actin filaments, running nearly parallel to each other and to the membrane, form a loose bundle of approximately 150 nm in diameter that “saddles” the inward-bending membrane at the leading edge of the division septum. The filaments do not make direct contact with the membrane. Our analysis of the actin filaments reveals the variability in filament number, nearest-neighbor distances between filaments within the bundle, their distance from the membrane and angular distribution with respect to the membrane.Significance StatementMost eukaryotic cells divide using a contractile actomyosin ring, but its structure is unknown. Here we use new specimen preparation methods and electron cryotomography to image constricting rings directly in 3D, in a near-native state in the model organism Schizosaccharomyces pombe. Our images reveal the arrangement of individual actin filaments within the contracting actomyosin ring.

scholarly journals Modeling myosin Va liposome transport through actin filament networks reveals a percolation threshold that modulates transport properties

2021 ◽  
Author(s):  
S. Walcott ◽  
D. M. Warshaw
Keyword(s):  
Phase Transition ◽  
Actin Filament ◽  
Actin Filaments ◽  
Three Dimensional ◽  
Fold Increase ◽  
Coarse Grained ◽  
Actin Network ◽  
Transport Distance ◽  
Myosin Va ◽  
Filament Networks

Myosin Va (myoVa) motors transport membrane-bound cargo through three-dimensional, intracellular actin filament networks. We developed a coarse-grained, in silico model to predict how actin filament density (3-800 filaments) within a randomly oriented actin network affects fluid-like liposome (350nm vs. 1,750nm) transport by myoVa motors. 5,000 simulated liposomes transported within each network adopted one of three states: transport, tug of war, or diffusion. Diffusion due to liposome detachment from actin rarely occurred given at least 10 motors on the liposome surface. However, with increased actin density, liposomes transitioned from primarily directed transport on single actin filaments to an apparent random walk, resulting from a mixture of transport and tug of wars as the probability of encountering additional actin filaments increased. This phase transition arises from a percolation phase transition at a critical number of accessible actin filaments, Nc. Nc is a geometric property of the actin network that depends only on the position and polarity of the actin filaments, transport distance, and the liposome diameter, as evidenced by a five-fold increase in liposome diameter resulting in a five-fold decrease in Nc. Thus, in cells, actin network density and cargo size may be regulated to match cargo delivery to the cell's physiological demands. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text]

scholarly journals Gating Mechanisms during Actin Filament Elongation by Formins

2018 ◽  
Author(s):  
Fikret Aydin ◽  
Naomi Courtemanche ◽  
Thomas D. Pollard ◽  
Gregory A. Voth
Keyword(s):  
Molecular Dynamics ◽  
Actin Filament ◽  
Actin Filaments ◽  
Coarse Grained ◽  
Gating Mechanisms ◽  
Helical Twist ◽  
Two Factors ◽  
Time Average ◽  
Coarse Grained Simulations ◽  
Dynamics Simulations

ABSTRACTFormins play an important role in the polymerization of unbranched actin filaments, and particular formins slow elongation by 5-95%. We studied the interactions between actin and the FH2 domains of formins Cdc12, Bni1 and mDia1 to understand the factors underlying their different rates of polymerization. All-atom molecular dynamics simulations revealed two factors that influence actin filament elongation and correlate with the rates of elongation. First, FH2 domains can sterically block the addition of new actin subunits. Second, FH2 domains flatten the helical twist of the terminal actin subunits, making the end less favorable for subunit addition. Coarse-grained simulations over longer time scales support these conclusions. The simulations show that filaments spend time in states that either allow or block elongation. The rate of elongation is a time-average of the degree to which the formin compromises subunit addition rather than the formin-actin complex literally being in ‘open’ or ‘closed’ states.

scholarly journals Coarse-grained simulations of bacterial cell wall growth reveal that local coordination alone can be sufficient to maintain rod shape

2015 ◽  
Vol 112 (28) ◽  
pp. E3689-E3698 ◽  
Author(s):  
Lam T. Nguyen ◽  
James C. Gumbart ◽  
Morgan Beeby ◽  
Grant J. Jensen
Keyword(s):  
Cell Wall ◽  
Failure Modes ◽  
Current Theory ◽  
Glycoside Hydrolases ◽  
Coarse Grained ◽  
Cell Integrity ◽  
Local Coordination ◽  
New Material ◽  
Coarse Grained Simulations ◽  
The Individual

Bacteria are surrounded by a peptidoglycan (PG) cell wall that must be remodeled to allow cell growth. While many structural details and properties of PG and the individual enzymes involved are known, how the process is coordinated to maintain cell integrity and rod shape is not understood. We have developed a coarse-grained method to simulate how individual transglycosylases, transpeptidases, and endopeptidases could introduce new material into an existing unilayer PG network. We find that a simple model with no enzyme coordination fails to maintain cell wall integrity and rod shape. We then iteratively analyze failure modes and explore different mechanistic hypotheses about how each problem might be overcome by the macromolecules involved. In contrast to a current theory, which posits that long MreB filaments are needed to coordinate PG insertion sites, we find that local coordination of enzyme activities in individual complexes can be sufficient to maintain cell integrity and rod shape. We also present possible molecular explanations for the existence of monofunctional transpeptidases and glycosidases (glycoside hydrolases), trimeric peptide crosslinks, cell twisting during growth, and synthesis of new strands in pairs.

scholarly journals Gating mechanisms during actin filament elongation by formins

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Fikret Aydin ◽  
Naomi Courtemanche ◽  
Thomas D Pollard ◽  
Gregory A Voth
Keyword(s):  
Molecular Dynamics ◽  
Actin Filament ◽  
Actin Filaments ◽  
Coarse Grained ◽  
Gating Mechanisms ◽  
Helical Twist ◽  
Two Factors ◽  
Time Average ◽  
Coarse Grained Simulations ◽  
Dynamics Simulations

Formins play an important role in the polymerization of unbranched actin filaments, and particular formins slow elongation by 5–95%. We studied the interactions between actin and the FH2 domains of formins Cdc12, Bni1 and mDia1 to understand the factors underlying their different rates of polymerization. All-atom molecular dynamics simulations revealed two factors that influence actin filament elongation and correlate with the rates of elongation. First, FH2 domains can sterically block the addition of new actin subunits. Second, FH2 domains flatten the helical twist of the terminal actin subunits, making the end less favorable for subunit addition. Coarse-grained simulations over longer time scales support these conclusions. The simulations show that filaments spend time in states that either allow or block elongation. The rate of elongation is a time-average of the degree to which the formin compromises subunit addition rather than the formin-actin complex literally being in ‘open’ or ‘closed’ states.

Electron Microscopy of Cytoplasmic Contractile Proteins

1978 ◽  
Vol 36 (3) ◽  
pp. 606-614 ◽  
Author(s):  
T.D. Pollard ◽  
P. Maupin
Keyword(s):  
Electron Microscopy ◽  
Actin Filaments ◽  
Three Dimensional ◽  
Uranyl Acetate ◽  
Contractile Proteins ◽  
Dimensional Structure ◽  
X Ray Diffraction ◽  
Cytoplasmic Matrix ◽  
Computer Image Processing ◽  
Nonmuscle Cells

In this paper we review some of the contributions that electron microscopy has made to the analysis of actin and myosin from nonmuscle cells. We place particular emphasis upon the limitations of the ultrastructural techniques used to study these cytoplasmic contractile proteins, because it is not widely recognized how difficult it is to preserve these elements of the cytoplasmic matrix for electron microscopy. The structure of actin filaments is well preserved for electron microscope observation by negative staining with uranyl acetate (Figure 1). In fact, to a resolution of about 3nm the three-dimensional structure of actin filaments determined by computer image processing of electron micrographs of negatively stained specimens (Moore et al., 1970) is indistinguishable from the structure revealed by X-ray diffraction of living muscle.

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