An exact approach for studying cargo transport by an ensemble of molecular motors.

Donatello Materassi
Donatello Materassi
Massachussets Institute of Technology
United States
Thomas Hays
Thomas Hays
University of Minnesota
United States

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.
PDF Download - Full Text Link
( Please be advised that this article is hosted on an external website not affiliated with
Source Status ListingPossible
November 2013
6 Reads

Similar Publications

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

PLoS Comput Biol 2016 Nov 3;12(11):e1005152. Epub 2016 Nov 3.

Department of Electrical Engineering, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States of America.

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. Read More

View Article
November 2016

How molecular motors are arranged on a cargo is important for vesicular transport.

PLoS Comput Biol 2011 May 5;7(5):e1002032. Epub 2011 May 5.

Department of Physics and Astronomy, University of California, Irvine, Irvine, California, United States of America.

The spatial organization of the cell depends upon intracellular trafficking of cargos hauled along microtubules and actin filaments by the molecular motor proteins kinesin, dynein, and myosin. Although much is known about how single motors function, there is significant evidence that cargos in vivo are carried by multiple motors. While some aspects of multiple motor function have received attention, how the cargo itself--and motor organization on the cargo--affects transport has not been considered. Read More

View Article
May 2011

Filament-filament switching can be regulated by separation between filaments together with cargo motor number.

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

View Article
August 2013

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

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.

We analyze theoretically the effects of excluded-volume interactions between motors on the dynamics of a cargo driven by multiple motors. The model considered shares much in common with others recently proposed in the literature, with the addition of direct interaction between motors and motor back steps. The cargo is assumed to follow a continuum Langevin dynamics, while individual motors evolve following a Monte Carlo algorithm based on experimentally accessible probabilities for discrete forward and backward jumps, and attachment and detachment rates. Read More

View Article
November 2010