Highly Loaded Behavior of Kinesins Increases the Robustness of Transport Under High Resisting Loads

Nam, Woochul; Epureanu, Bogdan I.

doi:10.1371/journal.pcbi.1003981

Cited by 18 publications

(17 citation statements)

References 38 publications

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“…Earlier theoretical studies have modeled cargo transport by multiple motors [21][22][23][24][25] but have not been able to predict the experimentally observed velocities and run times (average time to detachment) at high forces [17]. These models all assumed a symmetric force-detachment rate relation for a single kinesin; i.e., the detachment rate under assisting forces (applied in the stepping direction, positive) is equal to that under resisting or loading forces (applied against the stepping direction, negative).…”

mentioning

confidence: 99%

Force Generated by Two Kinesin Motors Depends on the Load Direction and Intermolecular Coupling

Khataee

Howard

2019

Phys. Rev. Lett.

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Kinesins are molecular motors that carry cellular cargoes. While the mechanics of single kinesins are well characterized experimentally, the behavior of multiple kinesins varies considerably among experiments. The basis for this variability is unknown. Here, we resolve single-motor force measurements into a vertical component, which accelerates kinesin detachment, and a horizontal component, which decelerates the detachment when resisting the motor. This directionality, when the different experimental geometries are considered, can account for much of the variation in multiple motor dynamics.

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confidence: 99%

Force Generated by Two Kinesin Motors Depends on the Load Direction and Intermolecular Coupling

Khataee

Howard

2019

Phys. Rev. Lett.

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“…Then, the unbinding probability of kinesin per step can be calculated by using A int as where is the unbinding probability per step when every neighboring binding site is not occupied by obstacles. are obtained from our previous model [ 45 ]. Δ P ub, obs is the change in the unbinding probability due to obstacles.…”

Section: Resultsmentioning

confidence: 99%

“…Δ P ub, obs is the change in the unbinding probability due to obstacles. Note that the kinesin dissociates from the MT mostly when one of its heads is diffusing [ 10 , 45 ]. Thus, it is assumed that the increase of the unbinding probability due to obstacles during that diffusion is also very large compared to Δ P ub, obs for other kinesin states.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, the velocity and run length are obtained again by using a stochastic mathematical model with the resolution of the experiments. The stochastic model was developed by integrating the diffusion model with a previously developed model which describes the stochastic motion of the kinesin in the absence of obstacles [ 45 ]. Details on the stochastic model are described in S1 File .…”

Section: Resultsmentioning

confidence: 99%

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Effects of Obstacles on the Dynamics of Kinesins, Including Velocity and Run Length, Predicted by a Model of Two Dimensional Motion

Nam¹,

Epureanu²

2016

PLoS ONE

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Kinesins are molecular motors which walk along microtubules by moving their heads to different binding sites. The motion of kinesin is realized by a conformational change in the structure of the kinesin molecule and by a diffusion of one of its two heads. In this study, a novel model is developed to account for the 2D diffusion of kinesin heads to several neighboring binding sites (near the surface of microtubules). To determine the direction of the next step of a kinesin molecule, this model considers the extension in the neck linkers of kinesin and the dynamic behavior of the coiled-coil structure of the kinesin neck. Also, the mechanical interference between kinesins and obstacles anchored on the microtubules is characterized. The model predicts that both the kinesin velocity and run length (i.e., the walking distance before detaching from the microtubule) are reduced by static obstacles. The run length is decreased more significantly by static obstacles than the velocity. Moreover, our model is able to predict the motion of kinesin when other (several) motors also move along the same microtubule. Furthermore, it suggests that the effect of mechanical interaction/interference between motors is much weaker than the effect of static obstacles. Our newly developed model can be used to address unanswered questions regarding degraded transport caused by the presence of excessive tau proteins on microtubules.

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“…The authors proposed that the increased run-length observed in the presence of two motors results from the lowered dissociation of each motor from the microtubule at decreased ATP concentrations and the increased probability that the cargo stayed bound to the microtubule. Studies such as [21, 29] using probabilistic models of single motors have also predicted in that an ensemble of kinesin motors is a robust system and the robustness increases under high loads [37]. …”

Section: Introductionmentioning

confidence: 99%

Interrogating Emergent Transport Properties for Molecular Motor Ensembles: A Semi-analytical Approach

Bhaban

Materassi

et al. 2016

PLoS Comput Biol

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Intracellular transport is an essential function in eucaryotic cells, facilitated by motor proteins—proteins converting chemical energy into kinetic energy. It is understood that motor proteins work in teams enabling unidirectional and bidirectional transport of intracellular cargo over long distances. Disruptions of the underlying transport mechanisms, often caused by mutations that alter single motor characteristics, are known to cause neurodegenerative diseases. For example, phosphorylation of kinesin motor domain at the serine residue is implicated in Huntington’s disease, with a recent study of phosphorylated and phosphomimetic serine residues indicating lowered single motor stalling forces. In this article we report the effects of mutations of this nature on transport properties of cargo carried by multiple wild-type and mutant motors. Results indicate that mutants with altered stall forces might determine the average velocity and run-length even when they are outnumbered by wild type motors in the ensemble. It is shown that mutants gain a competitive advantage and lead to an increase in the expected run-length when the load on the cargo is in the vicinity of the mutant’s stalling force or a multiple of its stalling force. A separate contribution of this article is the development of a semi-analytic method to analyze transport of cargo by multiple motors of multiple types. The technique determines transition rates between various relative configurations of motors carrying the cargo using the transition rates between various absolute configurations. This enables a computation of biologically relevant quantities like average velocity and run-length without resorting to Monte Carlo simulations. It can also be used to introduce alterations of various single motor parameters to model a mutation and to deduce effects of such alterations on the transport of a common cargo by multiple motors. Our method is easily implementable and we provide a software package for general use.

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Highly Loaded Behavior of Kinesins Increases the Robustness of Transport Under High Resisting Loads

Cited by 18 publications

References 38 publications

Force Generated by Two Kinesin Motors Depends on the Load Direction and Intermolecular Coupling

Force Generated by Two Kinesin Motors Depends on the Load Direction and Intermolecular Coupling

Effects of Obstacles on the Dynamics of Kinesins, Including Velocity and Run Length, Predicted by a Model of Two Dimensional Motion

Interrogating Emergent Transport Properties for Molecular Motor Ensembles: A Semi-analytical Approach

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