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An exact approach for studying cargo transport by an ensemble of molecular motors
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-prote...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879128/ https://www.ncbi.nlm.nih.gov/pubmed/24237658 http://dx.doi.org/10.1186/2046-1682-6-14 |
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author | Materassi, Donatello Roychowdhury, Subhrajit Hays, Thomas Salapaka, Murti |
author_facet | Materassi, Donatello Roychowdhury, Subhrajit Hays, Thomas Salapaka, Murti |
author_sort | Materassi, Donatello |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3879128 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-38791282014-01-08 An exact approach for studying cargo transport by an ensemble of molecular motors Materassi, Donatello Roychowdhury, Subhrajit Hays, Thomas Salapaka, Murti BMC Biophys Research Article 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. BioMed Central 2013-11-16 /pmc/articles/PMC3879128/ /pubmed/24237658 http://dx.doi.org/10.1186/2046-1682-6-14 Text en Copyright © 2013 Materassi et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Materassi, Donatello Roychowdhury, Subhrajit Hays, Thomas Salapaka, Murti An exact approach for studying cargo transport by an ensemble of molecular motors |
title | An exact approach for studying cargo transport by an ensemble of molecular motors |
title_full | An exact approach for studying cargo transport by an ensemble of molecular motors |
title_fullStr | An exact approach for studying cargo transport by an ensemble of molecular motors |
title_full_unstemmed | An exact approach for studying cargo transport by an ensemble of molecular motors |
title_short | An exact approach for studying cargo transport by an ensemble of molecular motors |
title_sort | exact approach for studying cargo transport by an ensemble of molecular motors |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879128/ https://www.ncbi.nlm.nih.gov/pubmed/24237658 http://dx.doi.org/10.1186/2046-1682-6-14 |
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