Tug-of-war between two elastically coupled molecular motors: a case study on force generation and force balance

Uçar, Mehmet Can; Lipowsky, Reinhard

doi:10.1039/c6sm01853j

Cited by 11 publications

(18 citation statements)

References 37 publications

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“…For two dyneins ( N − = 2) in a tug-of-war against a single kinesin motor ( N + = 1), for example, as depicted in Fig. 1, one needs to consider the activity state (2, 1) in which all three motors are bound to the filament, the state (2, 0) with two active dyneins 27 , the state (1, 1) with one active dynein and one active kinesin 28 , the states (1, 0) and (0, 1) corresponding to only one active motor, and the diffusive cargo state (0,0) with no active motors. We will consider motors from the same team to be distinguishable even if they are identical in the sense that they are built up from identical peptide chains.…”

Section: Resultsmentioning

confidence: 99%

“…For comparison, the predictions of the non-elastic model introduced by Müller, Klumpp, and Lipowsky (MKL) 5 are also included: in Fig. 5a,b the single kinesin is exposed to the average force whereas the two dyneins experience the same average force given by , equally sharing the force F ca experienced by the cargo 28 . In Fig.…”

Section: Resultsmentioning

confidence: 99%

“…For assisting forces F < 0, on the other hand, the velocity reaches its maximal value defined by v max for large negative F -values. The force-velocity relationship v ( F ) can be parametrized in terms of the velocity parameters v 0 , v min and v max as well as the stall force F s 27,28 for each motor species, which has the explicit form…”

Section: Model and Methodsmentioning

confidence: 99%

“…In order o obtain an expression for the stepping rates of a single motor, we first define the force-dependent forward-to-backward stepping ratio q ( F ) of a single motor. This ratio depends exponentially on the external force and was fitted by 27,28,49 with the zero-force stepping ratio q 0 = 800 for kinesin. For dynein, we use the estimate q 0 = 4 28 , in agreement with the stepping probabilities of yeast dynein measured by the Vale lab 31,32 .…”

Section: Model and Methodsmentioning

confidence: 99%

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Force sharing and force generation by two teams of elastically coupled molecular motors

Uçar

Lipowsky

2019

Sci Rep

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Many active cellular processes such as long-distance cargo transport, spindle organization, as well as flagellar and ciliary beating are driven by molecular motors. These motor proteins act collectively and typically work in small teams. One particularly interesting example is two teams of antagonistic motors that pull a common cargo into opposite directions, thereby generating mutual interaction forces. Important issues regarding such multiple motor systems are whether or not motors from the same team share their load equally, and how the collectively generated forces depend on the single motor properties. Here we address these questions by introducing a stochastic model for cargo transport by an arbitrary number of elastically coupled molecular motors. We determine the state space of this motor system and show that this space has a rather complex and nested structure, consisting of multiple activity states and a large number of elastic substates, even for the relatively small system of two identical motors working against one antagonistic motor. We focus on this latter case because it represents the simplest tug-of-war that involves force sharing between motors from the same team. We show that the most likely motor configuration is characterized by equal force sharing between identical motors and that the most likely separation of these motors corresponds to a single motor step. These likelihoods apply to different types of motors and to different elastic force potentials acting between the motors. Furthermore, these features are observed both in the steady state and during the initial build-up of elastic strains. The latter build-up is non-monotonic and exhibits a maximum at intermediate times, a striking consequence of mutual unbinding of the elastically coupled motors. Mutual strain-induced unbinding also reduces the magnitude of the collectively generated forces. Our computational approach is quite general and can be extended to other motor systems such as motor teams working against an optical trap or mixed teams of motors with different single motor properties.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Model and Methodsmentioning

confidence: 99%

Section: Model and Methodsmentioning

confidence: 99%

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Force sharing and force generation by two teams of elastically coupled molecular motors

Uçar

Lipowsky

2019

Sci Rep

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“…Various candidate proteins such as klar and JIP1 have been shown to modify transport behavior [1,3,16,[43][44][45][46][47][48][49][50]. Further, various other factors, such as memory effects during motor rebinding [19], interactions between multiple motors [51,52], variable dynein step sizes [21,53], and stochastic load sharing could also modify the transport behavior of the cargo. However we show using simulations incorporating a stochastic sharing of load between attached motors that the codependent behavior of cargo processivity is robust and is preserved even with additional inputs such as viscous friction and thermal noise (see Appendix A).…”

Section: Discussionmentioning

confidence: 99%

Dynein catch bond as a mediator of codependent bidirectional cellular transport

Puri

Gupta

Chandel

et al. 2019

Phys. Rev. Research

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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 counterintuitive observation, referred to as the paradox of codependence, is inconsistent with the existing paradigm of a mechanistic tug of war between oppositely directed motors. Unlike kinesin motors, dynein motors exhibit catch bonding, wherein the unbinding rates of these motors decrease with increasing force on them. Incorporating this catch-bonding behavior of dyneins in a theoretical model, we show that the functional divergence of the two motor species manifests itself as an internal regulatory mechanism, and leads to codependent-transport behavior in biologically relevant regimes. Using analytical methods and stochastic simulations, we analyze the processivity characteristics and probability distribution of run times and pause times of transported cellular cargoes. We show that catch bonding can drastically alter the transport characteristics and also provide a plausible resolution of the paradox of codependence.

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Coordination, cooperation, competition, crowding and congestion of molecular motors: Theoretical models and computer simulations

Sen,

Chowdhury,

Kunwar

2024

Advances in Protein Chemistry and Structural Biology

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Tug-of-war between two elastically coupled molecular motors: a case study on force generation and force balance

Cited by 11 publications

References 37 publications

Force sharing and force generation by two teams of elastically coupled molecular motors

Force sharing and force generation by two teams of elastically coupled molecular motors

Dynein catch bond as a mediator of codependent bidirectional cellular transport

Coordination, cooperation, competition, crowding and congestion of molecular motors: Theoretical models and computer simulations

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