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...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
BioMed Central Ltd
2014
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| Online Access: | http://hdl.handle.net/1721.1/84597 |
| _version_ | 1811092525026377728 |
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| author | Materassi, Donatello Roychowdhury, Subhrajit Hays, Thomas Salapaka, Murti |
| author2 | Massachusetts Institute of Technology. Laboratory for Information and Decision Systems |
| author_facet | Massachusetts Institute of Technology. Laboratory for Information and Decision Systems Materassi, Donatello Roychowdhury, Subhrajit Hays, Thomas Salapaka, Murti |
| author_sort | Materassi, Donatello |
| collection | MIT |
| 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. |
| first_indexed | 2024-09-23T15:19:35Z |
| format | Article |
| id | mit-1721.1/84597 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:19:35Z |
| publishDate | 2014 |
| publisher | BioMed Central Ltd |
| record_format | dspace |
| spelling | mit-1721.1/845972022-10-02T02:10:36Z An exact approach for studying cargo transport by an ensemble of molecular motors Materassi, Donatello Roychowdhury, Subhrajit Hays, Thomas Salapaka, Murti Massachusetts Institute of Technology. Laboratory for Information and Decision Systems Materassi, Donatello 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. National Science Foundation (U.S.) (Grant ECCS-1202411) 2014-01-27T19:15:27Z 2014-01-27T19:15:27Z 2013-11 2012-12 2013-12-23T00:21:01Z Article http://purl.org/eprint/type/JournalArticle 2046-1682 http://hdl.handle.net/1721.1/84597 Materassi, Donatello et al. “An Exact Approach for Studying Cargo Transport by an Ensemble of Molecular Motors.” BMC Biophysics 6.1 (2013): 14. en http://dx.doi.org/10.1186/2046-1682-6-14 BMC Biophysics Creative Commons Attribution http://creativecommons.org/licenses/by/2.0 Donatello Materassi et al.; licensee BioMed Central Ltd. application/pdf BioMed Central Ltd BioMed Central Ltd |
| spellingShingle | 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 |
| url | http://hdl.handle.net/1721.1/84597 |
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