Motor proteins transporting cargos

Processive motor proteins such as kinesin and myosin-V are enzymes that use the energy of ATP hydrolysis to travel along polar cytoskeletal filaments. One of the functions of these proteins is the transport of vesicles and protein complexes that are linked to the light chains of the motors. Modeling the light chain by a linear elastic spring, and using the two-state model for one- and two-headed molecular motors, we study the influence of thermal fluctuations of the cargo on the motion of the motor-cargo complex. We solve numerically the Fokker-Planck equations of motor motion, and find that the mean velocity of the motor-cargo complex decreases monotonously as the spring becomes softer. This effect is due to the random force of thermal fluctuations of the cargo disrupting the operation of the motor. Increasing the size (thus, the friction coefficient) of the cargo also decreases the velocity. Surprisingly, we find that for a given size of the cargo, the velocity has a maximum for a certain friction of the motor. We explain this effect by the interplay between the characteristic length of thermal fluctuations of the cargo on a spring, the motor diffusion length, and the filament period. Our results may be relevant for the interpretation of single-molecule experiments with molecular motors (bead assays), where the motor motion is observed by tracking of a bead attached to the motor.     

Effects of rebinding rate and asymmetry in unbinding rate on cargo transport by multiple kinesin motors

Many intracellular transports are performed by multiple molecular motors in a cooperative manner.Here,we use stochastic simulations to study the cooperative transport by multiple kinesin motors,focusing mainly on effects of the form of unbinding rate versus force and the rebinding rate of single motors on the cooperative transport.We consider two forms of the unbinding rate.One is the symmetric form with respect to the force direction,which is obtained according to Kramers theory.The other is the asymmetric form,which is obtained from the prior studies for the single kinesin motor.With the asymmetric form the simulated results of both velocity and run length of the cooperative transport by two identical motors and those by a kinesin-1 motor and a kinesin-2 motor are in quantitative agreement with the available experimental data,whereas with the symmetric form the simulated results are inconsistent with the experimental data.For the cooperative transport by a faster motor and a much slower motor,the asymmetric form can give both larger velocity and longer run length than the symmetric form,giving an explanation for why kinesin adopts the asymmetric form of the unbinding rate rather than the symmetric form.For the cooperative transport by two identical motors,while the velocity is nearly independent of the rebinding rate,the run length increases linearly with the rebinding rate.For the cooperative transport by two different motors,the increase of the rebinding rate of one motor also enhances the run length of the cooperative transport.The dynamics of transport by N(N=3,4,5,6,7 and 8)motors is also studied.     

Motility States of Molecular Motors Engaged in a Stochastic Tug-of-War

Intracellular transport is mediated by molecular motors that pull cargos along cytoskeletal filaments. Many cargos move bidirectionally and are transported by two teams of motors which move into opposite directions along the filament. We have recently introduced a stochastic tug-of-war model for this situation. This model describes the motion of the cargo as a Markov process on a two-dimensional state space defined by the numbers of active plus and active minus motors. In spite of its simplicity, this tug-of-war model leads to a complex dependence of the cargo motility on the motor parameters. We present new numerical results for the dependence on the number of involved motors. In addition, we derive a simple and intuitive sharp maxima approximation, from which one obtains the cargo motility state from only four simple inequalities. This approach provides a fast and reliable method to determine the cargo motility.     

Dynamics of cooperative transport by multiple kinesin motors and diffusing microtubule-associated proteins

In eukaryote cells, cargos are often transported cooperatively by kinesin motors and nonmotor microtubule-associated proteins (MAPs). The prior in vitro experimental data showed that the velocity of the cargo transported by kinesin motors and Ndc80 (a member of MAP) proteins of truncated coiled-coil stalks decreases sensitively with the increase of the ratio of Ndc80 to motor number. However, the underlying mechanism of Ndc80 affecting sensitively the cooperative cargo transport by kinesin motors is unclear. To understand the mechanism, here we study numerically the cooperative cargo transport by kinesin motors and Ndc80 proteins. Our results showed that for the case of the motors and Ndc80 proteins with truncated short stalks, as used in the experiments, the calculated results reproduce quantitatively the prior experimental data. The mechanism of the cargo velocity decreasing sensitively with the ratio of Ndc80 to motor number is revealed. By contrast, for the case of the motors and Ndc80 proteins with full-length long stalks, the velocity of the cargo decreases slowly with the increase in the ratio of Ndc80 to kinesin number. Our results thus give an explanation of why the kinesin motors working in the cell have long stalks.     

Energetics of molecular motor proteins: could it pay to take a free ride?

ABSTRACT

Molecular motor proteins are used in biological systems to generate directed motion. They consist of one end that can bind to and then move along a filament. The other end can then bind to a cargo that needs transporting and the motor then pulls it along. Here, we consider the energetics of this process allowing for the friction force exerted by the surrounding fluid, given that the process takes place in a confined geometry. In nature, not all motor/cargo complexes are bound to the filament, many are in solution. Here, we address the question of whether this can be energetically favourable given that the unbound complexes will be transported by the flow generated by those that are bound. A simple theory suggests that this is the case and that there exists an optimal coverage of bound complexes. Simulations of a model of this system that includes all the relevant hydrodynamic effects confirm that the assumptions in the theory are valid so long as the coverage of bound complexes is not too low. Using realistic values for the parameters involved yields an optimal coverage that is plausible for the biological systems involved.     

Symmetric linear potential and imperfect Brownian ratchet in molecular motor function

Biomolecular motors are tiny engines that transport materials at the microscopic level within biological cells. In recent years, Elston and Peskin et al have investigated the effect of the elastic properties of the tether that connects the motor to its cargo at the speed of the motor. In this paper we extend their work and present a tether in the form of symmetric linear potential.Our results show that when the driving mechanism is an imperfect Brownian ratchet, the average speed decreases as the stiffness of the tether increases in the limit of large motor diffusion coefficient, which is similar to the results of Elston and Peskin.However, a threshold for the stiffness of the tether connecting the motor to its cargo is found in our model. Only when the tether is stiffer than the threshold can the motor and its cargo function co-operatively, otherwise, the motor and its cargo depart from each other. This result is more realistic than that of the spring model of Elston and Peskin.     

The dynamics of cargo driven by molecular motors in the context of asymmetric simple exclusion processes

We consider the dynamics of cargo driven by a collection of interacting molecular motors in the context of an asymmetric simple exclusion process (ASEP). The model is formulated to account for (i) excluded-volume interactions, (ii) the observed asymmetry of the stochastic movement of individual motors and (iii) interactions between motors and cargo. Items (i) and (ii) form the basis of ASEP models and have already been considered to study the behavior of motor density profile [A. Parmeggiani, T. Franosch, E. Frey, Phase Coexistence in driven one-dimensional transport, Phys. Rev. Lett. 90 (2003) 086601-1-086601-4]. Item (iii) is new. It is introduced here as an attempt to describe explicitly the dependence of cargo movement on the dynamics of motors in this context. The steady-state solutions of the model indicate that the system undergoes a phase transition of condensation type as the motor density varies. We study the consequences of this transition to the behavior of the average cargo velocity.     

Molecular motors as cargo transporters in the cell—The good,the bad and the ugly

Single molecule properties of the cargo transporting processive molecular motors myosin-V, kinesin-1, and cytoplasmic dynein have been reported. These different classes of motors are known to cooperate during intracellular transport, and multiple motors (of same or different types) are simultaneously present on a given cellular cargo. However, differences in function are observed between these classes of motors—they have different force production ability, have a different average run length and step along their respective filaments using different size steps. Overall, the robustness of the motion they generate could be different. Is this apparent heterogeneity important for intracellular transport? Here we present a brief discussion of how the properties of these motors might be adapted to their coordinated function in vivo.     

A simplified tether model for molecular motor transporting cargo

Molecular motors are proteins or protein complexes which function as transporting engines in biological cells. This paper models the tether between motor and its cargo as a symmetric linear potential. Different from Elston and Peskin's work for which performance of the system was discussed only in some limiting cases, this study produces analytic solutions of the problem for general cases by simplifying the transport system into two physical states, which makes it possible to discuss the dynamics of the motor--cargo system in detail. It turns out that the tether strength between motor and cargo should be greater than a threshold or the motor will fail to transport the cargo, which was not discussed by former researchers yet. Value of the threshold depends on the diffusion coefficients of cargo and motor and also on the strength of the Brownian ratchets dragging the system. The threshold approaches a finite constant when the strength of the ratchet tends to infinity.     

Cooperativity of multiple kinesin-1 motors mechanically coupled through a shared load

Recent experiments using single-molecule techniques have characterized the mechanical properties of single kinesin molecules in vitro at a range of loads and ATP concentrations. These experiments have shown that kinesin moves processively along microtubules by alternately advancing each of its motor domains in a hand-over-hand fashion, using Brownian motion and the energy from ATP hydrolysis. We have extended the theoretical analysis of kinesin through a mechanistic model that is capable of describing transient and steady-state behavior. Transient dynamics are needed to describe the effect of external perturbations (e.g. interactions with other kinesin molecules). Quantitative metrics are tailored to characterize the synchronization of nonlinear, nonsmooth systems such as kinesin. These metrics are employed to analyze the simulation results and to quantify the effect of the cargo linker stiffness, the load, and the difference in intrinsic velocity on the synchronization of two coupled motor proteins. Herein, the mechanistic model and the new analysis techniques are demonstrated for the case of two coupled kinesin motors.     

Effect of kinesin velocity distribution on slow axonal transport

The goal of this paper is to investigate the effect that a distribution of kinesin motor velocities could have on cytoskeletal element (CE) concentration waves in slow axonal transport. Previous models of slow axonal transport based on the stop-and-go hypothesis (P. Jung, A. Brown, Modeling the slowing of neurofilament transport along the mouse sciatic nerve, Physical Biology 6 (2009) 046002) assumed that in the anterograde running state all CEs move with one and the same velocity as they are propelled by kinesin motors. This paper extends the aforementioned theoretical approach by allowing for a distribution of kinesin motor velocities; the distribution is described by a probability density function (PDF). For a two kinetic state model (that accounts for the pausing and running populations of CEs) an analytical solution describing the propagation of the CE concentration wave is derived. Published experimental data are used to obtain an analytical expression for the PDF characterizing the kinesin velocity distribution; this analytical expression is then utilized as an input for computations. It is demonstrated that accounting for the kinesin velocity distribution increases the rate of spreading of the CE concentration waves, which is a significant improvement in the two kinetic state model.     

Reduction of motor fan noise using CFD and CAA simulations

Motor fans used for cooling electric motors have long been recognized as one of the major noise sources. Current paper focuses on design of motor fan for electric motors that are used in submarines for pumping sea water. Noise reduction at source is very important and the critical task, for under water applications. An attempt has been made for reduction of motor fan noise by modification of noise sources. For this purpose computational fluid dynamics and computational aeroacoustics code FLUENT package is used to identify the noise sources and to know the overall sound pressure level of motor fan. From these results it is observed that aerodynamic noise is the dominate fan noise source. Aerodynamic noise of motor fan can be reduced by modifying fan geometry. The aerodynamic noise level of motor fan has been reduced by replacing the straight blades with various digits of NACA (National Advisory Committee for Aeronautics) 65 series airfoil sections. From the numerical results it is observed that the minimum sound pressure level for NACA 65-010 is 65.4 dB(A). These numerical results are compared with measurements in a semi-anechoic chamber. It is found that there is good agreement between numerical and experimental results.     

Collective alignment of polar filaments by molecular motors

We study the alignment of polar biofilaments, such as microtubules and actin, subject to the action of multiple molecular motors attached simultaneously to more than one filament. Focusing on a paradigm model of only two filaments interacting with multiple motors, we were able to investigate in detail the alignment dynamics. While almost no alignment occurs in the case of a single motor, the filaments become rapidly aligned due to the collective action of the motors. Our analysis shows that the alignment time is governed by the number of bound motors and the magnitude of the motors’ stepping fluctuations. We predict that the time scale of alignment is in the order of seconds, much faster than that reported for passive crosslink-induced bundling. In vitro experiments on the alignment of microtubules by multiple-motor covered beads are in qualitative agreement. We also discuss another mode of fast alignment of filaments, namely the cooperation between motors and passive crosslinks.     

Cooperative dynamics of coupled motor–cargoes system with stochastic interactions in the crowded environment

In this study, we investigate the cooperative transport behaviors of coupled motor–cargoes system, in which multiple passive cargoes stochastically interact with one active Brownian motor. The environment with stochastic interactions is characterized by the concentration (reflecting the cargo’s number in unit volume) and switching rate (reflecting the interacting stability between motor and cargoes), based on which the stationary multiple-state process can be employed to describe the fluctuating-cargo state in the coupled system. By analyzing the average probability current of decoupled system in the thermodynamic limit, we effectively study the possibility of cooperative transport through stochastic cargoes to behave rich dynamical behaviors, including the directed current, current reversal, stochastic resonance (SR) and stochastic inhibition (SI), inverse SR and SI, even without the effect of external driving force. Based on numerical results, we systematically discuss the transport dependence on various parameters, including the cargo concentration in the crowded environment, cargo capacity of the motor, driving amplitude of external periodic force, and medium temperature. Obviously, the sensitivity of transport process to parameter changes can be used by the environment to regulate its cargo traffic, which also provides latent support for manipulating the transport performance and optimizing the coupled structure in artificial nano-machines.     

Deformation in cooperative molecular motors

We implement a model to represent the effect of the deformation of the backbone of a system of motor proteins while sliding on a track filament. This model incorporates a nearest neighbor interaction term among the motors for the deformation energy. Correlations induced by this term result in increased motor force for inter-particle distances small compared to the ratchet period. Received 20 February 2001 and Received in final form 31 May 2001     

Collective Transport of Coupled Brownian Motors with Low Randomness

The transport properties of coupled Brownian motors in rocking ratchet are investigated via solving Langevin equation. By means of velocity, diffusion coefficient, and their ratio （Peclet number）, different features from a single particle have been found. In the regime of low-to-moderate D, the average velocity of elastically coupled Brownian motors is larger than that of a single Brownian particles; the Peclet number of elastically coupled Brownian motors is peaked functions of intensity of noise D but the Peclet number of a single Brownian motor decreases monotonously with the increase of a single Brownian motor. The results exhibit an interesting cooperative behavior between coupled particles subjected to a rocking force, which can generate directed transport with low randomness or high transport coherence in symmetrical periodic potential.     

Dynamic instability of collective myosin Ⅱ motors

Some kinds of muscles can oscillate spontaneously,which is related to the dynamic instability of the collective motors.Based on the two-state ratchet model and with consideration of the motor stiffness,the dynamics of collective myosin Ⅱmotors are studied.It is shown that when the motor stiffness is small,the velocity of the collective motors decreases monotonically with load increasing.When the motor stiffness becomes large,dynamic instability appears in the forcevelocity relationship of the collective-motor transport.For a large enough motor stiffness,the zero-velocity point lies in the unstable range of the force-velocity curve,and the motor system becomes unstable before the motion is stopped,so spontaneous oscillations can be generated if the system is elastically coupled to its environment via a spring.The oscillation frequency is related to the motor stiffness,motor binding rate,spring stiffness,and the width of the ATP excitation interval.For a medium motor stiffness,the zero-velocity point lies outside the unstable range of the force-velocity curve,and the motion will be stopped before the instability occurs.     

Role of Interactions and Correlations on Collective Dynamics of Molecular Motors Along Parallel Filaments

Cytoskeletal motors known as motor proteins are molecules that drive cellular transport along several parallel cytoskeletal filaments and support many biological processes. Experimental evidences suggest that they interact with the nearest molecules of their filament while performing any mechanical work. These interactions modify the microscopic level properties of motor proteins. In this work, a new version of two-channel totally asymmetric simple exclusion process, that incorporates the intra-channel interactions in a thermodynamically consistent way, is proposed. As the existing approaches for multi-channel systems deviate from analyzing the combined effect of inter and intra-channel interactions, a new approach known as modified vertical cluster mean field is developed. The approach along with Monte Carlo simulations successfully encounters some correlations and computes the complex dynamic properties of the system. Role of symmetry of interactions and inter-channel coupling is observed on the phase diagrams, maximal particle current and its corresponding optimal interaction strength. Surprisingly, for all values of coupling rate and most of the interaction splittings, the optimal interaction strength corresponding to maximal current belongs to the case of weak repulsive interactions. Moreover, for weak interaction splittings and with an increase in the coupling rate, the optimal interaction strength tends towards the known experimental results. The effect of coupling as well as interaction energy is also measured for correlations. They are found to be short-range and weaker for repulsive and weak attractive interactions while they are long-range and stronger for large attractions.