Force production by single kinesin motors

Biological Computation Research Department, Bell Laboratories, Lucent Technologies, Murray Hill, New Jersey 07974, USA.
Nature Cell Biology (Impact Factor: 19.68). 11/2000; 2(10):718-23. DOI: 10.1038/35036345
Source: PubMed


Motor proteins such as kinesin, myosin and polymerase convert chemical energy into work through a cycle that involves nucleotide hydrolysis. Kinetic rates in the cycle that depend upon load identify transitions at which structural changes, such as power strokes or diffusive motions, are likely to occur. Here we show, by modelling data obtained with a molecular force clamp, that kinesin mechanochemistry can be characterized by a mechanism in which a load-dependent isomerization follows ATP binding. This model quantitatively accounts for velocity data over a wide range of loads and ATP levels, and indicates that movement may be accomplished through two sequential 4-nm substeps. Similar considerations account for kinesin processivity, which is found to obey a load-dependent Michaelis-Menten relationship.

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    • "In general, this step is influenced by the load f (cargo weight) attached to the kinesin [34]. The next reaction describes the attachment of the free head domain β to the microtubule using an ADP molecule (D) and forming the complex M KT α D β . "
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    ABSTRACT: We discuss the implementation of a multiscale biophysico-chemical model able to cope with the main mechanisms underlying cumulative exocytosis in cells. The model is based on a diffusion equation in the presence of external forces that links calcium signaling and the biochemistry associated to the activity of cytoskeletal-based protein motors. This multiscale model offers an excellent quantitative spatio-temporal description of the cumulative exocytosis measured by means of fluorescence experiments. We also review pre-existing models reported in the literature on calcium waves, protein motor activation and dynamics, and intracellular directed transport of vesicles. As an example of the proposed model, we analyze the formation of the shield against polyspermy in the early events of fertilization in sea urchin eggs.
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    • "However, in all of the following models, we assume that the cargo transporting motors walk either on a single microtubule or on densely packed parallel microtubules. Thus, emerging forces will approximately act only parallel to the walking direction of the involved motors and the detachment rate will only depend on the absolute value of the applied force F and not on its direction [7] [9]. The attachment behavior is assumed to be independent of external forces. "
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    ABSTRACT: Intracellular cargos that are transported by groups of molecular motors often display bidirectional movement. This can be seen experimentally by tracking the trajectories of individual cargos in vivo. Typically, the cargo trajectories display many turning events that result from the stochastic nature of the involved motor processes. In this paper, we simulate cargo trajectories for different binding mechanisms. We introduce a series of statistical tools to analyze and quantitatively characterize these trajectories. As we demonstrate for specified single-motor properties, the novel statistical methods allow us to quantitatively distinguish between different models for bidirectional transport. In this way, the tools provide a quantitative connection between the statistical properties of the cargo trajectories and the molecular properties of the motor proteins. Such methods are also applicable to experimentally measured cargo trajectories and should be helpful in elucidating the mechanisms that lead to bidirectional transport.
    Physical Biology 01/2013; 10(1):016003. DOI:10.1088/1478-3975/10/1/016003 · 2.54 Impact Factor
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    • "4) is a usual assumption for the detachment rate in many models for transport by multiple motors [17], [18], [22], [23], [24], [25]. It provides a simple characterization of the detachment processes inspired by in vitro experiments with kinesin [39] and by the Kramers' theory for barrier crossing [40]. In the present work we assume such a simple formulation since there is no detailed knowledge of the detachment rates for kinesin 2 and dynein in melanophores. "
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    ABSTRACT: In this work, we explored theoretically the transport of organelles driven along microtubules by molecular motors of opposed polarities using a stochastic model that considers a Langevin dynamics for the cargo, independent cargo-motor linkers and stepping motion for the motors. It has been recently proposed that the stiffness of the motor plays an important role when multiple motors collectively transport a cargo. Therefore, we considered in our model the recently reported values for the stiffness of the cargo-motor linker determined in living cells (∼0.01 pN/nm, [1]) which is significantly lower than the motor stiffness obtained in in vitro assays and used in previous studies. Our model could reproduce the multimodal velocity distributions and typical trajectory characteristics including the properties of the reversions in the overall direction of motion observed during melanosome transport along microtubules in Xenopus laevis melanophores. Moreover, we explored the contribution of the different motility states of the cargo-motor system to the different modes of the velocity distributions and could identify the microscopic mechanisms of transport leading to trajectories compatible with those observed in living cells. Finally, by changing the attachment and detachment rates, the model could reproduce the different velocity distributions observed during melanosome transport along microtubules in Xenopus laevis melanophores stimulated for aggregation and dispersion. Our analysis suggests that active tug-of-war processes with loose mechanical coupling can account for several aspects of cargo transport along microtubules in living cells.
    PLoS ONE 08/2012; 7(8):e43599. DOI:10.1371/journal.pone.0043599 · 3.23 Impact Factor
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