scholarly journals Bond type and discretization of non-muscle myosin II are critical for simulated contractile dynamics

2019 ◽  
Author(s):  
D.B Cortes ◽  
M. Gordon ◽  
F. Nédélec ◽  
A.S. Maddox
Keyword(s):  
Molecular Motors ◽  
Cell Shape ◽  
Molecular Motor ◽  
Myosin Ii ◽  
Coarse Graining ◽  
Agent Based ◽  
Bond Type ◽  
Relative Contribution ◽  
Trade Offs ◽  
Muscle Myosin

ABSTRACTMolecular motors drive cytoskeletal rearrangements to change cell shape. Myosins are the motors that move, crosslink, and modify the actin cytoskeleton. The primary force generator in contractile actomyosin networks is non-muscle myosin II (NMMII), a molecular motor that assembles into ensembles that bind, slide, and crosslink actin filaments (F-actin). The multivalence of NMMII ensembles and their multiple roles have confounded the resolution of crucial questions including how the number of NMMII subunits affects dynamics, and what affects the relative contribution of ensembles’ crosslinking versus motoring activities. Since biophysical measurements of ensembles are sparse, modeling of actomyosin networks has aided in discovering the complex behaviors of NMMII ensembles. Myosin ensembles have been modeled via several strategies with variable discretization/coarse-graining and unbinding dynamics, and while general assumptions that simplify motor ensembles result in global contractile behaviors, it remains unclear which strategies most accurately depict cellular activity. Here, we used an agent-based platform, Cytosim, to implement several models of NMMII ensembles. Comparing the effects of bond type, we found that ensembles of catch-slip and catch motors were the best force generators and binders of filaments. Slip motor ensembles were capable of generating force but unbound frequently, resulting in slower contractile rates of contractile networks. Coarse-graining of these ensemble types from two sets of 16 motors on opposite ends of a stiff rod to two binders, each representing 16 motors, reduced force generation, contractility, and the total connectivity of filament networks for all ensemble types. A parallel cluster model (PCM) previously used to describe ensemble dynamics via statistical mechanics, allowed better contractility with coarse-graining, though connectivity was still markedly reduced for this ensemble type with coarse-graining. Together our results reveal substantial trade-offs associated with the process of coarse-graining NMMII ensembles and highlight the robustness of discretized catch-slip ensembles in modeling actomyosin networks.STATEMENT OF SIGNIFICANCEAgent-based simulations of contractile networks allow us to explore the mechanics of actomyosin contractility, which drives many cell shape changes including cytokinesis, the final step of cell division. Such simulations should be able to predict the mechanics and dynamics of non-muscle contractility, however recent work has highlighted a lack of consensus on how to best model the non-muscle myosin II. These ensembles of approximately 32 motors are the key components responsible for driving contractility. Here, we explored different methods for modeling non-muscle myosin II ensembles within the context of contractile actomyosin networks. We show that the level of coarse-graining and the choice of unbinding model used to model motor unbinding under load indeed has profound effects on contractile network dynamics.

Molecular Motors: Force and Movement Generated by Single Myosin II Molecules

Physiology ◽  
2002 ◽  
Vol 17 (5) ◽  
pp. 213-218 ◽  
Author(s):  
Caspar Rüegg ◽  
Claudia Veigel ◽  
Justin E. Molloy ◽  
Stephan Schmitz ◽  
John C. Sparrow ◽  
...  
Keyword(s):  
Optical Tweezers ◽  
Single Molecule ◽  
Molecular Motors ◽  
Molecular Motor ◽  
Myosin Ii ◽  
Force Production ◽  
Myosin Isoforms ◽  
Single Molecule Level ◽  
Recent Developments ◽  
Muscle Myosin

Muscle myosin II is an ATP-driven, actin-based molecular motor. Recent developments in optical tweezers technology have made it possible to study movement and force production on the single-molecule level and to find out how different myosin isoforms may have adapted to their specific physiological roles.

scholarly journals Positional isomers of a non-nucleoside substrate differentially affect myosin function

2019 ◽  
Author(s):  
M. Woodward ◽  
E. Ostrander ◽  
S.P. Jeong ◽  
X. Liu ◽  
B. Scott ◽  
...  
Keyword(s):  
Energy Source ◽  
Muscle Contraction ◽  
Motor Function ◽  
Molecular Motors ◽  
Molecular Motor ◽  
Vesicular Transport ◽  
Gain Control ◽  
Mechanical Work ◽  
Chemical Energy ◽  
Muscle Myosin

AbstractMolecular motors have evolved to transduce chemical energy from adenosine triphosphate into mechanical work to drive essential cellular processes, from muscle contraction to vesicular transport. Dysfunction of these motors is a root cause of many pathologies necessitating the need for intrinsic control over molecular motor function. Herein, we demonstrate that positional isomerism can be used as a simple and powerful tool to control the molecular motor of muscle, myosin. Using three isomers of a synthetic non-nucleoside triphosphate we demonstrate that myosin’s force and motion generating capacity can be dramatically altered at both the ensemble and single molecule levels. By correlating our experimental results with computation, we show that each isomer exerts intrinsic control by affecting distinct steps in myosin’s mechano-chemical cycle. Our studies demonstrate that subtle variations in the structure of an abiotic energy source can be used to control the force and motility of myosin without altering myosin’s structure.Statement of SignificanceMolecular motors transduce chemical energy from ATP into the mechanical work inside a cell, powering everything from muscle contraction to vesicular transport. While ATP is the preferred source of energy, there is growing interest in developing alternative sources of energy to gain control over molecular motors. We synthesized a series of synthetic compounds to serve as alternative energy sources for muscle myosin. Myosin was able to use this energy source to generate force and velocity. And by using different isomers of this compound we were able to modulate, and even inhibit, the activity of myosin. This suggests that changing the isomer of the substrate could provide a simple, yet powerful, approach to gain control over molecular motor function.

scholarly journals Linking the Landscape of MYH9-Related Diseases to the Molecular Mechanisms that Control Non-Muscle Myosin II-A Function in Cells

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1458 ◽  
Author(s):  
Gloria Asensio-Juárez ◽  
Clara Llorente-González ◽  
Miguel Vicente-Manzanares
Keyword(s):  
Molecular Mechanisms ◽  
Clinical Presentation ◽  
Molecular Motor ◽  
Myosin Ii ◽  
Residual Activity ◽  
Cellular Level ◽  
Actin Binding ◽  
Compensatory Mechanisms ◽  
Myh9 Gene ◽  
Muscle Myosin

The MYH9 gene encodes the heavy chain (MHCII) of non-muscle myosin II A (NMII-A). This is an actin-binding molecular motor essential for development that participates in many crucial cellular processes such as adhesion, cell migration, cytokinesis and polarization, maintenance of cell shape and signal transduction. Several types of mutations in the MYH9 gene cause an array of autosomal dominant disorders, globally known as MYH9-related diseases (MYH9-RD). These include May-Hegglin anomaly (MHA), Epstein syndrome (EPS), Fechtner syndrome (FTS) and Sebastian platelet syndrome (SPS). Although caused by different MYH9 mutations, all patients present macrothrombocytopenia, but may later display other pathologies, including loss of hearing, renal failure and presenile cataracts. The correlation between the molecular and cellular effects of the different mutations and clinical presentation are beginning to be established. In this review, we correlate the defects that MYH9 mutations cause at a molecular and cellular level (for example, deficient filament formation, altered ATPase activity or actin-binding) with the clinical presentation of the syndromes in human patients. We address why these syndromes are tissue restricted, and the existence of possible compensatory mechanisms, including residual activity of mutant NMII-A and/or the formation of heteropolymers or co-polymers with other NMII isoforms.

A Dynamic Escape Problem of Molecular Motors

2020 ◽  
Vol 142 (5) ◽  
Author(s):  
Dean Culver ◽  
Bryan Glaz ◽  
Samuel Stanton
Keyword(s):  
Molecular Motors ◽  
Binding Sites ◽  
Molecular Motor ◽  
Myosin Ii ◽  
Three Dimensional ◽  
Production Capacity ◽  
Force Production ◽  
Actin Binding ◽  
Three Dimensional Model ◽  
Thermal Agitation

Abstract Animal skeletal muscle exhibits very interesting behavior at near-stall forces (when the muscle is loaded so strongly that it can barely contract). Near this physical limit, the myosin II proteins may be unable to reach advantageous actin binding sites through simple attractive forces. It has been shown that the advantageous utilization of thermal agitation is a likely source for an increased force-production capacity and reach in myosin-V (a processing motor protein), and here we explore the dynamics of a molecular motor without hand-over-hand motion including Brownian motion to show how local elastic energy well boundaries may be overcome. We revisit a spatially two-dimensional mechanical model to illustrate how thermal agitation can be harvested for useful mechanical work in molecular machinery inspired by this biomechanical phenomenon without rate functions or empirically inspired spatial potential functions. Additionally, the model accommodates variable lattice spacing, and it paves the way for a full three-dimensional model of cross-bridge interactions where myosin II may be azimuthally misaligned with actin binding sites. With potential energy sources based entirely on realizable components, this model lends itself to the design of artificial, molecular-scale motors.

scholarly journals Drosophila non-muscle myosin II motor activity determines the rate of tissue folding

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Claudia G Vasquez ◽  
Sarah M Heissler ◽  
Neil Billington ◽  
James R Sellers ◽  
Adam C Martin
Keyword(s):  
Motor Activity ◽  
Molecular Motor ◽  
Myosin Ii ◽  
Cell Contractility ◽  
Myosin Motor ◽  
Muscle Myosin ◽  
Shape Changes ◽  
Drosophila Embryos

Non-muscle cell contractility is critical for tissues to adopt shape changes. Although, the non-muscle myosin II holoenzyme (myosin) is a molecular motor that powers contraction of actin cytoskeleton networks, recent studies have questioned the importance of myosin motor activity cell and tissue shape changes. Here, combining the biochemical analysis of enzymatic and motile properties for purified myosin mutants with in vivo measurements of apical constriction for the same mutants, we show that in vivo constriction rate scales with myosin motor activity. We show that so-called phosphomimetic mutants of the Drosophila regulatory light chain (RLC) do not mimic the phosphorylated RLC state in vitro. The defect in the myosin motor activity in these mutants is evident in developing Drosophila embryos where tissue recoil following laser ablation is decreased compared to wild-type tissue. Overall, our data highlights that myosin activity is required for rapid cell contraction and tissue folding in developing Drosophila embryos.

scholarly journals Two Motors and One Spring: Hypothetic Roles of Non-Muscle Myosin II and Submembrane Actin-Based Cytoskeleton in Cell Volume Sensing

2021 ◽  
Vol 22 (15) ◽  
pp. 7967
Author(s):  
Nadezhda Barvitenko ◽  
Muhammad Aslam ◽  
Alfons Lawen ◽  
Carlota Saldanha ◽  
Elisaveta Skverchinskaya ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Ionic Strength ◽  
Cell Volume ◽  
Molecular Motors ◽  
Actin Polymerization ◽  
Myosin Ii ◽  
Regulatory Volume Decrease ◽  
Membrane Curvature ◽  
Actin Cortex ◽  
Muscle Myosin

Changes in plasma membrane curvature and intracellular ionic strength are two key features of cell volume perturbations. In this hypothesis we present a model of the responsible molecular apparatus which is assembled of two molecular motors [non-muscle myosin II (NMMII) and protrusive actin polymerization], a spring [a complex between the plasma membrane (PM) and the submembrane actin-based cytoskeleton (smACSK) which behaves like a viscoelastic solid] and the associated signaling proteins. We hypothesize that this apparatus senses changes in both the plasma membrane curvature and the ionic strength and in turn activates signaling pathways responsible for regulatory volume increase (RVI) and regulatory volume decrease (RVD). During cell volume changes hydrostatic pressure (HP) changes drive alterations in the cell membrane curvature. HP difference has opposite directions in swelling versus shrinkage, thus allowing distinction between them. By analogy with actomyosin contractility that appears to sense stiffness of the extracellular matrix we propose that NMMII and actin polymerization can actively probe the transmembrane gradient in HP. Furthermore, NMMII and protein-protein interactions in the actin cortex are sensitive to ionic strength. Emerging data on direct binding to and regulating activities of transmembrane mechanosensors by NMMII and actin cortex provide routes for signal transduction from transmembrane mechanosensors to cell volume regulatory mechanisms.

scholarly journals A model of processive walking and slipping of kinesin-8 molecular motors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ping Xie
Keyword(s):  
Single Molecule ◽  
Molecular Motors ◽  
External Load ◽  
Molecular Motor ◽  
Velocity Versus ◽  
Stick Slip ◽  
Load Dependence ◽  
Chemomechanical Coupling ◽  
Similarities And Differences ◽  
Stick Slip Motion

AbstractKinesin-8 molecular motor can move with superprocessivity on microtubules towards the plus end by hydrolyzing ATP molecules, depolymerizing microtubules. The available single molecule data for yeast kinesin-8 (Kip3) motor showed that its superprocessive movement is frequently interrupted by brief stick–slip motion. Here, a model is presented for the chemomechanical coupling of the kinesin-8 motor. On the basis of the model, the dynamics of Kip3 motor is studied analytically. The analytical results reproduce quantitatively the available single molecule data on velocity without including the slip and that with including the slip versus external load at saturating ATP as well as slipping velocity versus external load at saturating ADP and no ATP. Predicted results on load dependence of stepping ratio at saturating ATP and load dependence of velocity at non-saturating ATP are provided. Similarities and differences between dynamics of kinesin-8 and that of kinesin-1 are discussed.

Continuum model of epithelial morphogenesis during Caenorhabditis elegans embryonic elongation

2009 ◽  
Vol 367 (1902) ◽  
pp. 3379-3400 ◽  
Author(s):  
P. Ciarletta ◽  
M. Ben Amar ◽  
M. Labouesse
Keyword(s):  
Caenorhabditis Elegans ◽  
Epithelial Cells ◽  
Molecular Motor ◽  
Biomechanical Model ◽  
Epithelial Morphogenesis ◽  
Embryonic Cells ◽  
Microtubule Network ◽  
Theoretical Predictions ◽  
Elongation Process ◽  
Muscle Myosin

The purpose of this work is to provide a biomechanical model to investigate the interplay between cellular structures and the mechanical force distribution during the elongation process of Caenorhabditis elegans embryos. Epithelial morphogenesis drives the elongation process of an ovoid embryo to become a worm-shaped embryo about four times longer and three times thinner. The overall anatomy of the embryo is modelled in the continuum mechanics framework from the structural organization of the subcellular filaments within epithelial cells. The constitutive relationships consider embryonic cells as homogeneous materials with an active behaviour, determined by the non-muscle myosin II molecular motor, and a passive viscoelastic response, related to the directional properties of the filament network inside cells. The axisymmetric elastic solution at equilibrium is derived by means of the incompressibility conditions, the continuity conditions for the overall embryo deformation and the balance principles for the embryonic cells. A particular analytical solution is proposed from a simplified geometry, demonstrating the mechanical role of the microtubule network within epithelial cells in redistributing the stress from a differential contraction of circumferentially oriented actin filaments. The theoretical predictions of the biomechanical model are discussed within the biological scenario proposed through genetic analysis and pharmacological experiments.

scholarly journals Non-muscle myosin II drives vesicle loss during human reticulocyte maturation

Haematologica ◽  
2018 ◽  
Vol 103 (12) ◽  
pp. 1997-2007 ◽  
Author(s):  
Pedro L. Moura ◽  
Bethan R. Hawley ◽  
Tosti J. Mankelow ◽  
Rebecca E. Griffiths ◽  
Johannes G.G. Dobbe ◽  
...  
Keyword(s):  
Myosin Ii ◽  
Reticulocyte Maturation ◽  
Muscle Myosin

scholarly journals Non-muscle myosin II in kidney morphogenesis

2017 ◽  
Vol 13 (7) ◽  
pp. 384-384
Author(s):  
Katharine H. Wrighton
Keyword(s):  
Myosin Ii ◽  
Kidney Morphogenesis ◽  
Muscle Myosin
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