Within cells, vesicles and proteins are actively transported several micrometers along the cytoskeletal filaments. The transport along microtubules is propelled by dynein and kinesin motors, which carry the cargo in opposite directions. Bidirectional intracellular transport is performed with great efficiency, even under strong confinement, as for example in the axon. For this kind of transport system, one would expect generically cluster formation. In this work, we discuss the effect of the recently observed self-enhanced binding-affinity along the kinesin trajectories on the MT. We introduce a stochastic lattice-gas model, where the enhanced binding affinity is realized via a floor-field. From Monte Carlo simulations and a mean-field analysis we show that this mechanism can lead to self-organized symmetry-breaking and lane-formation which indeed leads to efficient bidirectional transport in narrow environments.
KIF1A kinesins are single-headed motor proteins which move on cylindrical nano-tubes called microtubules (MT). A normal MT consists of 13 protofilaments on which the equispaced motor binding sites form a periodic array. The collective movement of the kinesins on a MT is, therefore, analogous to vehicular traffic on multi-lane highways where each protofilament is the analogue of a single lane. Does lane-changing increase or decrease the motor flux per lane? We address this fundamental question here by appropriately extending a recent model [{\it Phys. Rev. E {\bf 75}, 041905 (2007)}]. By carryi…
Intracellular cargos which are transported by molecular motors move stochastically along cytoskeleton filaments. In particular for bidirectionally transported cargos it is an open question whether the characteristics of their motion can result from pure stochastic fluctuations or whether some coordination of the motors is needed. The results of a mean-field model of cargo-motors dynamics, which was proposed by Müller et al.[1] suggest the existence of high motility states which would result from a stochastic tug-of-war. Here we analyze a non-mean field extension of their model, that takes expl…
Inside cells, various cargos are transported by teams of molecular motors. Intriguingly, the motors involved generally have opposite pulling directions, and the resulting cargo dynamics is a biased stochastic motion. It is an open question how the cell can control this bias. Here we develop a model which takes explicitly into account the elastic coupling of the cargo with each motor. We show that bias can be simply controlled or even reversed in a counterintuitive manner via a change in the external force exerted on the cargo or a variation of the ATP binding rate to motors. Furthermore, the s…
We discuss a theoretical model for bidirectional cargo transport in biological cells, which is driven by teams of molecular motors and subject to thermal fluctuations. The model describes explicitly the directed motion of the molecular motors on the filament. The motor-cargo coupling is implemented via linear springs. By means of extensive Monte Carlo simulations we show that the model describes the experimentally observed regimes of anomalous diffusion, i.e. subdiffusive behavior at short times followed by superdiffusion at intermediate times. The model results indicate that subdiffuse regime…
Motor protein motion on biopolymers can be described by models related to the totally asymmetric simple exclusion process (TASEP). Inspired by experiments on the motion of kinesin-4 motors on antiparallel microtubule overlaps, we analyze a model incorporating the TASEP on two antiparallel lanes with binding kinetics and lane switching. We determine the steady-state motor density profiles using phase plane analysis of the steady-state mean field equations and kinetic Monte Carlo simulations. We focus on the the density-density phase plane, where we find an analytic solution to the mean-field mo…
Intracellular bidirectional transport of cargo on microtubule filaments is achieved by the collective action of oppositely directed dynein and kinesin motors. Experiments have found that in certain cases, inhibiting the activity of one type of motor results in an overall decline in the motility of the cellular cargo in both directions. This counter-intuitive observation, referred to as {\em paradox of codependence} is inconsistent with the existing paradigm of a mechanistic tug-of-war between oppositely directed motors. Unlike kinesin, dynein motors exhibit catchbonding, wherein the unbinding …
In this paper, we introduce an ASEP-like transport model for bidirectional motion of particles on a multi-lane lattice. The model is motivated by {\em in vivo} experiments on organelle motility along a microtubule (MT), consisting of thirteen protofilaments, where particles are propelled by molecular motors (dynein and kinesin). In the model, organelles (particles) can switch directions of motion due to "tug-of-war" events between counteracting motors. Collisions of particles on the same lane can be cleared by switching to adjacent protofilaments (lane changes). We analyze transport properties…
Cytoplasmic dynein exhibits a directional processive movement on microtubule filaments and is known to move in steps of varying length based on the number of ATP molecules bound to it and the load that it carries. It is experimentally observed that dynein takes occasional backward steps and the frequency of such backward steps increases as the load approaches the stall force. Using a stochastic process model, we investigate the bidirectional movement of single head of a dynein motor. The probability for backward step is implemented based on Crook's fluctuation theorem of non-equilibrium statis…
We analyze the collective behavior of hydrodynamically coupled molecular motors. We show that the local fluxes induced by motors displacement can induce the experimentally observed bidirectional motion of cargoes and vesicles. By means of a mean--field approach we show that sustained oscillations as well as bistable collective motor motion arise even for very large collection of motors, when thermal noise is irrelevant. The analysis clarifies the physical mechanisms responsible for such dynamics by identifying the relevant coupling parameter and its dependence on the geometry of the hydrodynam…
Intracellular transport processes driven by molecular motors can be described by stochastic lattice models of self-driven particles. Here we focus on bidirectional transport models excluding the exchange of particles on the same track. We explore the possibility to have efficient transport in these systems. One possibility would be to have appropriate interactions between the various motors' species, so as to form lanes. However, we show that the lane formation mechanism based on modified attachment/detachment rates as it was proposed previously is not necessarily connected to an efficient tra…
The cooperative action of many molecular motors is essential for dynamic processes such as cell motility and mitosis. This action can be studied by using motility assays in which the motion of cytoskeletal filaments over a surface coated with motor proteins is tracked. In previous studies of actin-myosin II systems, fast directional motion was observed, reflecting the tendency of myosin II motors to propagate unidirectionally along actin filaments. Here, we present a motility assay with actin bundles consisting of short filamentous segments with randomly alternating polarities. These actin tra…
Molecular motor proteins serve as an essential component of intracellular transport by generating forces to haul cargoes along cytoskeletal filaments. Two species of motors that are directed oppositely (e.g. kinesin, dynein) can be attached to the same cargo, which is known to produce bidirectional net motion. Although previous work focuses on the motor number as the driving noise source for switching, we propose an alternative mechanism: cargo diffusion. A mean-field mathematical model of mechanical interactions of two populations of molecular motors with cargo thermal fluctuations (diffusion…
We study the role of microtubule movement in bidirectional organelle transport in Drosophila S2 cells and show that EGFP-tagged peroxisomes in cells serve as sensitive probes of motor induced, noisy cytoskeletal motions. Multiple peroxisomes move in unison over large time windows and show correlations with microtubule tip positions, indicating rapid microtubule fluctuations in the longitudinal direction. We report the first high-resolution measurement of longitudinal microtubule fluctuations performed by tracing such pairs of co-moving peroxisomes. The resulting picture shows that motor-depend…
Bidirectional variants of stochastic many particle models for transport by molecular motors show a strong tendency to form macroscopic clusters on static lattices. Inspired by the fact that the microscopic tracks for molecular motors are dynamical, we study the influence of different types of lattice dynamics on stochastic bidirectional transport. We observe a transition toward efficient transport (corresponding to the dissolution of large clusters) controlled by the lattice dynamics.
Many biological processes involve the action of molecular motors that interact with the cell cytoskeleton. Some processes, such as the transport of cargoes is achieved mainly by the action of individual motors. Other, such as cell motility and division, require the cooperative work of many motors. Collective motor dynamics can be quite complex and unexpected. One beautiful example is the bidirectional ("back and forth") motion of filaments which is induced when the motors within a group exert forces in opposite directions. This review tackles the puzzle emerging from a recent experimental work…
Bidirectional cargo transport by molecular motors in cells is a complex phenomenon, in which the cargo (usually a vesicle) alternately moves in retrograde and anterograde directions. In this case, teams of oppositely pulling motors (eg., kinesin and dynein) bind to the cargo simultaneously, and `coordinate' their activity such that the motion consists of spells of positively and negatively directed segments, separated by pauses of varying duration. A set of recent experiments have analyzed the bidirectional motion of endosomes in the amoeba D. discoideum in detail. It was found that in between…
We use a two-state ratchet model to study the cooperative bidirectional motion of molecular motors on cytoskeletal tracks with randomly alternating polarities. Our model is based on a previously proposed model [Badoual et al., {\em Proc. Natl. Acad. Sci. USA} {\bf 99}, 6696 (2002)] for collective motor dynamics and, in addition, takes into account the cooperativity effect arising from the elastic tension that develops in the cytoskeletal track due to the joint action of the walking motors. We show, both computationally and analytically, that this additional cooperativity effect leads to a dram…
Most models designed to study the bidirectional movement of cargos as they are driven by molecular motors rely on the idea that motors of different polarities can be coordinated by external agents if arranged into a motor-cargo complex to perform the necessary work [gross04]. Although these models have provided us with important insights into these phenomena, there are still many unanswered questions regarding the mechanisms through which the movement of the complex takes place on crowded microtubules. For example (i) how does cargo-binding affect motor motility? and in connection with that - …
Many different types of cellular cargos are transported bidirectionally along microtubules by teams of molecular motors. The motion of this cargo-motors system has been experimentally characterized in vivo as processive with rather persistent directionality. Different theoretical approaches have been suggested in order to explore the origin of this kind of motion. An effective theoretical approach, introduced by Müller et al., describes the cargo dynamics as a tug-of-war between different kinds of motors. An alternative approach has been suggested recently by Kunwar et al., who considered the …
In eukaryotic cells, motor proteins (MP) bind to cytoskeletal filaments and move along them in a directed manner generating active stresses. During cell division a spindle structure of overlapping antiparallel microtubules (MT) form whose stability and dynamics under the influence of MPs has been studied extensively. Although passive cross linkers (PCL) were known to provide structural stability to filamentous network, consequences of the interplay between ATP dependent active forces of MPs and passive entropic forces of PCLs on MT overlap remains largely unexplored. Here, we formulate and cha…
Here we generalize our previous model of molecular motors trafficking subdiffusing cargos in viscoelastic cytosol by (i) including mechanochemical coupling between cyclic conformational fluctuations of the motor protein driven by the reaction of ATP hydrolysis and its translational motion within the simplest two-state model of hand-over-hand motion of kinesin, and also (ii) by taking into account the anharmonicity of the tether between the motor and cargo (its maximally possible extension length). It is shown that the major earlier results such as occurrence of normal versus anomalous transpor…
We present a simple model for the bidirectional dynamics of actin bundles with alternating polarities in gliding assays with non-processive myosin motors. In the model, the bundle is represented as an elastic chain consisting of monomers with positive and negative polarities. The motion of the bundle is induced by the pulling forces of the underlying motors which stochastically attach to the monomers and, depending on the polarity of the monomers, pull them in the right or left direction. We demonstrate that perfectly a-polar chains consisting of equal numbers of monomers with positive and neg…
Molecular motors are essential components for the biophysical functions of the cell. Our current quantitative understanding of how multiple motors move along a single track is not complete; even though models and theories for single motor chemomechanics abound. Recently, M.J.I. M$\ddot{\rm u}$ller {\em et al.} have developed a tug-of-war model to describe the bidirectional movement of the cargo (PNAS(2008) 105(12) P4609-4614). Through Monte Carlo simulations, they discovered that the tug-of-war model exhibits several qualitative different motility regimes, which depend on the precise value of …
We present a computer simulation study, via lattice Boltzmann simulations, of a microscopic model for cytoplasmic streaming in algal cells such as those of Chara corallina. We modelled myosin motors tracking along actin lanes as spheres undergoing directed motion along fixed lines. The sphere dimension takes into account the fact that motors drag vesicles or other organelles, and, unlike previous work, we model the boundary close to which the motors move as walls with a finite slip layer. By using realistic parameter values for actin lane and myosin density, as well as for endoplasmic and vacu…
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 investigate a driven two-channel system where particles on different lanes mutually obstruct each others motion extending an earlier model by Popkov and Peschel [1]. This obstruction may occur in biological contexts due to steric hinderance where motor proteins carry cargos by `walking' on microtubules. Similarly, the model serves as a description for classical spin transport where charged particles with internal states move unidirectionally on a lattice. Three regimes of qualitatively different behavior are identified depending on the strength of coupling between the lanes. For small and l…
Recent experiments have demonstrated that dynein motor exhibits catch bonding behaviour, in which the unbinding rate of a single dynein decreases with increasing force, for a certain range of force. Motivated by these experiments, we propose a model for catch bonding in dynein using a threshold force bond deformation (TFBD) model wherein catch bonding sets in beyond a critical applied load force. We study the effect of catch bonding on unidirectional transport properties of cellular cargo carried by multiple dynein motors within the framework of this model. We find catch bonding can result in …
Motor-driven cargo transport is a complex phenomenon where multiple motor proteins attached on to a cargo engage in pulling activity, often leading to tug-of-war, displaying bidirectional motion. However, most mathematical and computational models ignore the details of the motor-cargo interaction. Here, we study a generic model in which N motors are elastically coupled to a cargo, which itself is subjected to thermal noise in the cytoplasm and to an additional external applied force. The motor-hopping rates are chosen to satisfy detailed balance with respect to the energy of elastic stretching…
We study a minimal lattice model which describes bidirectional transport of "particles" driven along a one dimensional track, as is observed in microtubule based, motor protein driven bidirectional transport of cargo vesicles, lipid bodies and organelles such as mitochondria. This minimal model, a multi-species totally asymmetric exclusion process (TASEP) with directional switching, can provide a framework for understanding the interplay between the switching dynamics of individual particles and the collective movement of particles in 1-dimension. When switching is much faster than translocati…
The totally asymmetric simple exclusion process (TASEP) is a paradigmatic stochastic model for non-equilibrium physics, and has been successfully applied to describe active transport of molecular motors along cytoskeletal filaments. Building on this simple model, we consider a two-lane lattice-gas model that couples directed transport (TASEP) to diffusive motion in a semi-closed geometry, and simultaneously accounts for spontaneous growth and particle-induced shrinkage of the system's size. This particular extension of the TASEP is motivated by the question of how active transport and diffusio…
