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    An exact approach for studying cargo transport by an ensemble of molecular motors.
    BMC Biophys 2013 Nov 16;6(1):14. Epub 2013 Nov 16.
    Laboratory for Information and Decision Systems, Massachussets Institute of Technology, 77 Massachusetts Avenue Cambridge, MA 02139, USA.
    Background: Intracellular transport is crucial for many cellular processes where a large fraction of the cargo is transferred by motor-proteins over a network of microtubules. Malfunctions in the transport mechanism underlie a number of medical maladies.Existing methods for studying how motor-proteins coordinate the transfer of a shared cargo over a microtubule are either analytical or are based on Monte-Carlo simulations. Approaches that yield analytical results, while providing unique insights into transport mechanism, make simplifying assumptions, where a detailed characterization of important transport modalities is difficult to reach. On the other hand, Monte-Carlo based simulations can incorporate detailed characteristics of the transport mechanism; however, the quality of the results depend on the number and quality of simulation runs used in arriving at results. Here, for example, it is difficult to simulate and study rare-events that can trigger abnormalities in transport.

    Results: In this article, a semi-analytical methodology that determines the probability distribution function of motor-protein behavior in an exact manner is developed. The method utilizes a finite-dimensional projection of the underlying infinite-dimensional Markov model, which retains the Markov property, and enables the detailed and exact determination of motor configurations, from which meaningful inferences on transport characteristics of the original model can be derived.

    Conclusions: Under this novel probabilistic approach new insights about the mechanisms of action of these proteins are found, suggesting hypothesis about their behavior and driving the design and realization of new experiments.The advantages provided in accuracy and efficiency make it possible to detect rare events in the motor protein dynamics, that could otherwise pass undetected using standard simulation methods. In this respect, the model has allowed to provide a possible explanation for possible mechanisms under which motor proteins could coordinate their motion.

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    Department of Electrical Engineering, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States of America.
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    Department of Physics and Astronomy, University of California, Irvine, Irvine, California, United States of America.
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    PLoS One 2013 14;8(2):e54298. Epub 2013 Feb 14.
    Department of Physics and Astronomy, University of California Irvine, Irvine, California, United States of America.
    How intracellular transport controls the probability that cargos switch at intersections between filaments is not well understood. In one hypothesis some motors on the cargo attach to one filament while others attach to the intersecting filament, and the ensuing tug-of-war determines which filament is chosen. We investigate this hypothesis using 3D computer simulations, and discover that switching at intersections increases with the number of motors on the cargo, but is not strongly dependent on motor number when the filaments touch. Read More
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    Phys Biol 2010 Nov 22;7(4):046009. Epub 2010 Nov 22.
    Dpto de Física de la Materia Condensada and BIFI, Universidad de Zaragoza, 50009 Zaragoza, Spain.
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