scholarly journals Processivity of molecular motors under vectorial loads

2020 ◽  
Author(s):  
Hamid Khataee ◽  
Zoltan Neufeld ◽  
Mohammed Mahamdeh
Keyword(s):  
Molecular Motors ◽  
Molecular Motor ◽  
Average Distance ◽  
Three Dimensional ◽  
Transition Rates ◽  
Spatial Organisation ◽  
Load Dependence ◽  
Detachment Rate ◽  
Kinetic Transition ◽  
Load Angle

AbstractMolecular motors are cellular machines that drive the spatial organisation of the cells by transporting cargoes along intracellular filaments. Although the mechanical properties of single molecular motors are relatively well characterised, it remains elusive how the three-dimensional geometry of a load imposed on a motor affects its processivity, i.e., the average distance that a motor moves per interaction with a filament. Here, we theoretically explore this question for a single kinesin molecular motor by analysing the load-dependence of the stepping and detachment processes. We find that the processivity of kinesin increases with lowering the load angle between kinesin and microtubule filament, due to the deceleration of the detachment rate. When the load angle is large, the processivity is predicted to enhance with accelerating the stepping rate, through an optimal distribution of the load over the kinetic transition rates underlying a mechanical step of the motor. These results provide new insights into understanding of the design of potential synthetic biomolecular machines that can travel long distances with high velocities.

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.

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 Molecular motor-driven filament transport across three-dimensional, polymeric micro-junctions

2021 ◽  
Author(s):  
Cordula Reuther ◽  
Sönke Steenhusen ◽  
Christoph Meinecke ◽  
pradheebha surendiran ◽  
Aseem Salhotra ◽  
...  
Keyword(s):  
Molecular Motors ◽  
Molecular Motor ◽  
Three Dimensional ◽  
Two Dimensions ◽  
Transport Systems ◽  
Focal Volume ◽  
Lab On Chip ◽  
Glass Substrates ◽  
Organic Hybrid ◽  
On Chip

Abstract Molecular motor-driven filament systems have been extensively explored for biomedical and nanotechnological applications such as lab-on-chip molecular detection or network-based biocomputation. In these applications, filament transport conventionally occurs in two dimensions (2D), often guided along open, topographically and/or chemically structured channels which are coated by molecular motors. However, at crossing points of different channels the filament direction is less well determined and, though crucial to many applications, reliable guiding across the junction can often not be guaranteed. We here present a three-dimensional (3D) approach that eliminates the possibility for filaments to take wrong turns at junctions by spatially separating the channels crossing each other. Specifically, 3D junctions with tunnels and overpasses were manufactured on glass substrates by two-photon polymerization, a 3D fabrication technology where a tightly focused, femtosecond-pulsed laser is scanned in a layer-to-layer fashion across a photo-polymerizable inorganic-organic hybrid polymer (ORMOCER®) with µm resolution. Solidification of the polymer was confined to the focal volume, enabling the manufacturing of arbitrary 3D microstructures according to CAD data. Successful realization of the 3D junction design was verified by optical and electron microscopy. Most importantly, we demonstrated the reliable transport of filaments, namely microtubules propelled by kinesin-1 motors, across these 3D junctions without junction errors. Our results open up new possibilities for 3D functional elements in biomolecular transport systems, in particular their implementation in biocomputational networks.

DIRECTED MOTION OF BROWNIAN MOTORS: A RATCHET MODEL OF TWO-COUPLED MOLECULAR MOTORS

2007 ◽  
Vol 21 (28) ◽  
pp. 1915-1921 ◽  
Author(s):  
SHUTANG WEN ◽  
HONGWEI ZHANG ◽  
LEIAN LIU ◽  
XIAOFENG SUN ◽  
YUXIAO LI
Keyword(s):  
Molecular Motors ◽  
Particle System ◽  
Langevin Equations ◽  
Transition Rates ◽  
Neck Length ◽  
Directed Motion ◽  
Mean Velocity ◽  
Positive Direction ◽  
Brownian Motors ◽  
The Individual

We investigated the motion of two-head Brownian motors by introducing a model in which the two heads coupled through an elastic spring is subjected to a stochastic flashing potential. The ratchet potential felt by the individual head is anti-correlated. The mean velocity was calculated based on Langevin equations. It turns out that we can obtain a unidirectional current. The current is sensitive to the transition rates and neck length and other parameters. The coupling of transition rate and neck length leads to variations both in the values and directions of currency. With a larger neck length, the bi-particle system has a larger velocity in one direction, while with a smaller neck length, it has a smaller velocity in the other direction. This is very likely the case of myosins with a larger neck length and larger velocity in the positive direction of filaments and kinesins with a smaller neck length and smaller velocity in the negative direction of microtubules. We also further investigated how current reversal depended on the neck length and the transition rates.

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 Molecular mechanisms for microtubule length regulation by kinesin-8 and XMAP215 proteins

2014 ◽  
Vol 4 (6) ◽  
pp. 20140031 ◽  
Author(s):  
Louis Reese ◽  
Anna Melbinger ◽  
Erwin Frey
Keyword(s):  
Molecular Motors ◽  
Molecular Mechanisms ◽  
Molecular Motor ◽  
Mutual Exclusion ◽  
High Growth ◽  
Dependent Manner ◽  
Dynamic Regulation ◽  
Filament Dynamics ◽  
Length Regulation ◽  
The Stability

The cytoskeleton is regulated by a plethora of enzymes that influence the stability and dynamics of cytoskeletal filaments. How microtubules (MTs) are controlled is of particular importance for mitosis, during which dynamic MTs are responsible for proper segregation of chromosomes. Molecular motors of the kinesin-8 protein family have been shown to depolymerize MTs in a length-dependent manner, and recent experimental and theoretical evidence suggests a possible role for kinesin-8 in the dynamic regulation of MTs. However, so far the detailed molecular mechanisms of how these molecular motors interact with the growing MT tip remain elusive. Here we show that two distinct scenarios for the interactions of kinesin-8 with the MT tip lead to qualitatively different MT dynamics, including accurate length control as well as intermittent dynamics. We give a comprehensive analysis of the regimes where length regulation is possible and characterize how the stationary length depends on the biochemical rates and the bulk concentrations of the various proteins. For a neutral scenario, where MTs grow irrespective of whether the MT tip is occupied by a molecular motor, length regulation is possible only for a narrow range of biochemical rates, and, in particular, limited to small polymerization rates. By contrast, for an inhibition scenario, where the presence of a motor at the MT tip inhibits MT growth, the regime where length regulation is possible is extremely broad and includes high growth rates. These results also apply to situations where a polymerizing enzyme like XMAP215 and kinesin-8 mutually exclude each other from the MT tip. Moreover, we characterize the differences in the stochastic length dynamics between the two scenarios. While for the neutral scenario length is tightly controlled, length dynamics is intermittent for the inhibition scenario and exhibits extended periods of MT growth and shrinkage. On a broader perspective, the set of models established in this work quite generally suggest that mutual exclusion of molecules at the ends of cytoskeletal filaments is an important factor for filament dynamics and regulation.

scholarly journals Extension of mathematical background for Nearest Neighbour Analysis in three-dimensional space

2013 ◽  
Vol 11 ◽  
pp. 25-36
Author(s):  
Eva Stopková
Keyword(s):  
Dimensional Space ◽  
Average Distance ◽  
Three Dimensional ◽  
Nearest Neighbour ◽  
Mathematical Background ◽  
Area Of Interest ◽  
Nearest Neighbours ◽  
Anisotropic Function ◽  
Neighbour Analysis ◽  
Three Dimensional Space

Proceeding deals with development and testing of the module for GRASS GIS [1], based on Nearest Neighbour Analysis. This method can be useful for assessing whether points located in area of interest are distributed randomly, in clusters or separately. The main principle of the method consists of comparing observed average distance between the nearest neighbours r A to average distance between the nearest neighbours r E that is expected in case of randomly distributed points. The result should be statistically tested. The method for two- or three-dimensional space differs in way how to compute r E . Proceeding also describes extension of mathematical background deriving standard deviation of r E , needed in statistical test of analysis result. As disposition of phenomena (e.g. distribution of birds’ nests or plant species) and test results suggest, anisotropic function would repre- sent relationships between points in three-dimensional space better than isotropic function that was used in this work.

scholarly journals Active and Unidirectional Acceleration of Biaryl Rotation by a Molecular Motor

2019 ◽  
Author(s):  
Edgar Uhl ◽  
Peter Mayer ◽  
Henry Dube
Keyword(s):  
Potential Energy ◽  
Motor Unit ◽  
Rate Constants ◽  
Molecular Motors ◽  
Molecular Motor ◽  
Molecular Machine ◽  
Single Bond ◽  
Bond Rotation ◽  
Immense Potential

Light driven molecular motors possess immense potential as central driving units for future nanotechnology. Integration into larger molecular setups and transduction of their mechanical motions represents the current frontier of research. Here we report on an integrated molecular machine setup allowing to transmit potential energy from a motor unit unto a remote receiving entity. The setup consists of a motor unit connected covalently to a distant and sterically strongly encumbered biaryl receiver. By action of the motor unit single bond rotation of the receiver is strongly accelerated and forced to proceed unidirectionally. The transmitted potential energy is directly measured as the extent to which energy degeneration is lifted in the thermal atropisomerization of this biaryl. Energy degeneracy is reduced by as much as 2.3 kcal/mol and rate accelerations up to 2x10<sup>5</sup> fold in terms of rate constants are achieved.<br><b></b>

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 Cilia oscillations

2019 ◽  
Vol 375 (1792) ◽  
pp. 20190157 ◽  
Author(s):  
Yi Man ◽  
Feng Ling ◽  
Eva Kanso
Keyword(s):  
Feedback Control ◽  
Motor Activity ◽  
Molecular Motors ◽  
Molecular Motor ◽  
Control Model ◽  
Eukaryotic Cells ◽  
Sperm Number ◽  
Sliding Motion ◽  
Molecular Machinery ◽  
Oscillation Frequencies

Cilia, or eukaryotic flagella, are microscopic active filaments expressed on the surface of many eukaryotic cells, from single-celled protozoa to mammalian epithelial surfaces. Cilia are characterized by a highly conserved and intricate internal structure in which molecular motors exert forces on microtubule doublets causing cilia oscillations. The spatial and temporal regulations of this molecular machinery are not well understood. Several theories suggest that geometric feedback control from cilium deformations to molecular activity is needed. Here, we implement a recent sliding control model, where the unbinding of molecular motors is dictated by the sliding motion between microtubule doublets. We investigate the waveforms exhibited by the model cilium, as well as the associated molecular motor dynamics, for hinged and clamped boundary conditions. Hinged filaments exhibit base-to-tip oscillations while clamped filaments exhibit both base-to-tip and tip-to-base oscillations. We report the change in oscillation frequencies and amplitudes as a function of motor activity and sperm number, and we discuss the validity of these results in the context of experimental observations of cilia behaviour. This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.

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