The influence of direct motor–motor interaction in models for cargo transport by a single team of motors

Bouzat, Sebastián; Falo, Fernando

doi:10.1088/1478-3975/7/4/046009

Cited by 36 publications

(112 citation statements)

References 28 publications

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“…Alteration in motor number is only one way how the power for motion in a given direction might be modulated, as it is possible to vary the force produced by a single motor [8]. (C) Opposing motors are simultaneously attached to the cargo, but a complex coordination machinery (pink) ensures that when one motor is actively engaged with the microtubule, the other motor is turned off [47,83]. The coordination machinery might be the target of trans-acting regulators.…”

Section: How Is Directionality Determined?mentioning

confidence: 99%

See 1 more Smart Citation

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

2015

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Cells are the elementary units of living organisms, which are able to carry out many vital functions. These functions rely on active processes on a microscopic scale. Therefore, they are strongly out-of-equilibrium systems, which are driven by continuous energy supply. The tasks that have to be performed in order to maintain the cell alive require transportation of various ingredients, some being small, others being large. Intracellular transport processes are able to induce concentration gradients and to carry objects to specific targets. These processes cannot be carried out only by diffusion, as cells may be crowded, and quite elongated on molecular scales. Therefore active transport has to be organized.The cytoskeleton, which is composed of three types of filaments (microtubules, actin and intermediate filaments), determines the shape of the cell, and plays a role in cell motion. It also serves as a road network for a special kind of vehicles, namely the cytoskeletal motors. These molecules can attach to a cytoskeletal filament, perform directed motion, possibly carrying along some cargo, and then detach.It is a central issue to understand how intracellular transport driven by molecular motors is regulated. The interest for this type of question was enhanced when it was discovered that intracellular transport breakdown is one of the signatures of some neuronal diseases like the Alzheimer.We give a survey of the current knowledge on microtubule based intracellular transport. Our review includes on the one hand an overview of biological facts, obtained from experiments, and on the other hand a presentation of some modeling attempts based on cellular automata. We present some background knowledge on the original and variants of the TASEP (Totally Asymmetric Simple Exclusion Process), before turning to more application oriented models. After addressing microtubule based transport in general, with a focus on in vitro experiments, and on cooperative effects in the transportation of large cargos by multiple motors, we concentrate on axonal transport, because of its relevance for neuronal diseases. Some important characteristics of axonal transport is that it takes place in a confined environment; Besides several types of motors are involved, that move in opposite directions. It is a challenge to understand how this bidirectional transport is organized. We review several features that could contribute to the efficiency of bidirectional transport in the axon, including in particular the role of motor-motor interactions and of the dynamics of the underlying microtubule network. Finally, we also discuss some open questions that may be relevant for future research in this field.

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Section: How Is Directionality Determined?mentioning

confidence: 99%

“…Such models were developped for cargos driven either by one type of motors [209,47] or by two types of opposite motors [215,48,49,194] -the latter being the case of interest here for us. The comparison between these stochastic models and the mean-field model revealed strong differences in the dynamics [48].…”

Section: Tug-of-warmentioning

confidence: 99%

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

2015

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“…These approaches typically take one of two roads: They either start by splitting the state with two bound motors, C 2 into several substates, 7,14,19,20,37,57,61 in which case some results can still be obtained analytically, or use detailed computational models that particularly emphasize on the geometry of the motor-complex or the arrangement of motors on a bead. 13,39,41 In reference, 37 a detailed chemomechanical network for two-motor complexes is used to generate trajectories and to show that the parameters 2 and v 2 can be deduced in a unique manner from the statistical properties of the trajectories. As mentioned already in the introduction, there exist considerable differences between the predictions obtained from different models with respect to interference effects.…”

Section: General Theoretical Frameworkmentioning

confidence: 99%

“…[50][51][52] In addition, several groups have developed models that include detailed descriptions of the single motors involved and that address specific effects such as the stochasticity of stepping 19,41,42 and the geometry of motor assemblies. 13,20,21,40 As in the experimental studies listed above, the focus of recent theoretical work has been on assemblies of two motor molecules. In particular, several recent studies have addressed the model case of two coupled kinesin-1 motors.…”

Section: Introductionmentioning

confidence: 99%

Elastic Coupling Effects in Cooperative Transport by a Pair of Molecular Motors

et al. 2012

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Abstract-Engineered constructs coupling a defined number of molecular motors provide an opportunity to study the cooperative transport of cargoes. Theoretical descriptions for the dynamics of such complexes can help to understand experimental data or to quantitatively formulate expectations for such experiments and provide a general framework for such analysis. Here, we review and extend recent theoretical studies that focused on pairs of molecular motors to study effects of coupling between the motors. We derive explicit results for two elastically coupled kinesin-1 motors as a function of the coupling strength using both linear and nonlinear springs. In addition, we discuss the general dynamics of such motor pairs, which is governed by characteristic time scales for the spontaneous unbinding of motors and for the built-up of strain forces that are sufficiently large to affect the run length and/or the velocity of the motors. We show how the comparison of these time scales can be used to predict the distinct behavior of different motor species, the effects of coupling, and the impact of the single motor velocity on the observable dynamics of a motor pair.

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“…Several studies have appeared in the last few years, based (mostly) on Hookean spring-like interaction between motor and the cargo [19,20,21,22,23,24,25,26,27,28,29]. In Kunwar et al [20], along with elastic interaction among the motors, non-linear force-velocity relations are assigned to different motors.…”

Section: Introductionmentioning

confidence: 99%

Transport of organelles by elastically coupled motor proteins

Bhat

Gopalakrishnan

2016

Eur. Phys. J. E

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Abstract. Motor-driven intracellular transport is a complex phenomenon where multiple motor proteins simultaneously 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. A few studies have focused on more realistic models of cargo transport by including elastic motor-cargo coupling, but either restrict the number of motors and/or use purely phenomenological forms for force-dependent hopping rates. 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. With these assumptions, an (N + 1)− variable master equation is constructed for dynamics of the motor-cargo complex. By expanding the hopping rates to linear order in fluctuations in motor positions, we obtain a linear Fokker-Planck equation. The deterministic equations governing the average quantities are separated out and explicit analytical expressions are obtained for the mean velocity and diffusion coefficient of the cargo. We also study the statistical features of the force experienced by an individual motor and quantitatively characterize the load-sharing among the cargo-bound motors. The mean cargo velocity and the effective diffusion coefficient are found to be decreasing functions of the stiffness. While increase in the number of motors N does not increase the velocity substantially, it decreases the effective diffusion coefficient which falls as 1/N asymptotically. We further show that the cargo-bound motors share the force exerted on the cargo equally only in the limit of vanishing elastic stiffness; as stiffness is increased, deviations from equal load sharing are observed. Numerical simulations agree with our analytical results where expected. Interestingly, we find in simulations that the stall force of a cargo elastically coupled to motors is independent of the stiffness of the linkers. PACS

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The influence of direct motor–motor interaction in models for cargo transport by a single team of motors

Cited by 36 publications

References 28 publications

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Elastic Coupling Effects in Cooperative Transport by a Pair of Molecular Motors

Transport of organelles by elastically coupled motor proteins

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