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.

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 Acto-myosin cross-bridge stiffness depends on the nucleotide state of the myosin II

2020 ◽  
Author(s):  
Tianbang Wang ◽  
Bernhard Brenner ◽  
Arnab Nayak ◽  
Mamta Amrute-Nayak
Keyword(s):  
Single Molecule ◽  
Mechanical Performance ◽  
Myosin Ii ◽  
Myosin Isoforms ◽  
Cross Bridge ◽  
Contraction Speed ◽  
Prolonged Duration ◽  
Trapping Method ◽  
Muscle Types ◽  
Muscle Myosin

AbstractHow various myosin isoforms fulfill the diverse physiological requirements of distinct muscle types remains unclear. Myosin II isoforms expressed in skeletal muscles determines the mechanical performance of the specific muscles as fast movers, or slow movers but efficient force holders. Here, we employed a single-molecule optical trapping method and compared the chemo-mechanical properties of slow and fast muscle myosin II isoforms. Stiffness of the myosin motor is key to its force-generating ability during muscle contraction. We found that acto-myosin (AM) cross-bridge stiffness depends on its nucleotide state as the myosin progress through the ATPase cycle. The strong actin bound ‘AM.ADP’ state exhibited > 2 fold lower stiffness than ‘AM rigor’ state. The two myosin isoforms displayed similar ‘rigor’ stiffness. We conclude that the time-averaged stiffness of the slow myosin is lower due to prolonged duration of the AM.ADP state, which determines the force-generating potential and contraction speed of the muscle, elucidating the basis for functional diversity among myosins.

scholarly journals POTATO: An automated pipeline for batch analysis of optical tweezers data

2021 ◽  
Author(s):  
Stefan Buck ◽  
Lukas Pekarek ◽  
Neva Caliskan
Keyword(s):  
Data Analysis ◽  
Optical Tweezers ◽  
Single Molecule ◽  
Molecular Motors ◽  
Analysis Tool ◽  
Recent Developments ◽  
Protein Nucleic Acid ◽  
Programming Knowledge ◽  
Nucleic Acid Interactions ◽  
User Friendly

Optical tweezers is a single-molecule technique that allows probing of intra- and intermolecular interactions that govern complex biological processes involving molecular motors, protein-nucleic acid interactions and protein/RNA folding. Recent developments in instrumentation eased and accelerated optical tweezers data acquisition, but analysis of the data remains challenging. Here, to enable high-throughput data analysis, we developed an automated python-based analysis pipeline called POTATO (Practical Optical Tweezers Analysis TOol). POTATO automatically processes the high-frequency raw data generated by force-ramp experiments and identifies (un)folding events using predefined parameters. After segmentation of the force-distance trajectories at the identified (un)folding events, sections of the curve can be fitted independently to worm-like chain and freely-jointed chain models, and the work applied on the molecule can be calculated by numerical integration. Furthermore, the tool allows plotting of constant force data and fitting of the Gaussian distance distribution over time. All these features are wrapped in a user-friendly graphical interface (https://github.com/REMI-HIRI/POTATO), which allows researchers without programming knowledge to perform sophisticated data analysis.

scholarly journals Kinetic Characterization of Non-Muscle Myosin IIB Single-Headed Heavy Meromyosin on Single Molecule Level with Optical Tweezers

2010 ◽  
Vol 98 (3) ◽  
pp. 561a
Author(s):  
Attila Nagy ◽  
Yasuharu Takagi ◽  
Earl E. Homsher ◽  
Davin K.T. Hong ◽  
Mihaly Kovacs ◽  
...  
Keyword(s):  
Optical Tweezers ◽  
Single Molecule ◽  
Kinetic Characterization ◽  
Heavy Meromyosin ◽  
Single Molecule Level ◽  
Muscle Myosin

scholarly journals Molecular motors: forty years of interdisciplinary research

2011 ◽  
Vol 22 (21) ◽  
pp. 3936-3939 ◽  
Author(s):  
James A. Spudich
Keyword(s):  
Single Molecule ◽  
Molecular Motors ◽  
Atp Hydrolysis ◽  
Molecular Motor ◽  
Single Molecule Level ◽  
In Vitro Motility ◽  
Nonmuscle Cell ◽  
Nonmuscle Cells ◽  
City Plan

A mere forty years ago it was unclear what motor molecules exist in cells that could be responsible for the variety of nonmuscle cell movements, including the “saltatory cytoplasmic particle movements” apparent by light microscopy. One wondered whether nonmuscle cells might have a myosin-like molecule, well known to investigators of muscle. Now we know that there are more than a hundred different molecular motors in eukaryotic cells that drive numerous biological processes and organize the cell's dynamic city plan. Furthermore, in vitro motility assays, taken to the single-molecule level using techniques of physics, have allowed detailed characterization of the processes by which motor molecules transduce the chemical energy of ATP hydrolysis into mechanical movement. Molecular motor research is now at an exciting threshold of being able to enter into the realm of clinical applications.

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.

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.

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.

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