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Cargo surface fluidity can reduce inter-motor mechanical interference, promote load-sharing and enhance processivity in teams of molecular motors
In cells, multiple molecular motors work together as teams to carry cargoes such as vesicles and organelles over long distances to their destinations by stepping along a network of cytoskeletal filaments. How motors that typically mechanically interfere with each other, work together as teams is unc...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9212169/ https://www.ncbi.nlm.nih.gov/pubmed/35675381 http://dx.doi.org/10.1371/journal.pcbi.1010217 |
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author | Sarpangala, Niranjan Gopinathan, Ajay |
author_facet | Sarpangala, Niranjan Gopinathan, Ajay |
author_sort | Sarpangala, Niranjan |
collection | PubMed |
description | In cells, multiple molecular motors work together as teams to carry cargoes such as vesicles and organelles over long distances to their destinations by stepping along a network of cytoskeletal filaments. How motors that typically mechanically interfere with each other, work together as teams is unclear. Here we explored the possibility that purely physical mechanisms, such as cargo surface fluidity, may potentially enhance teamwork, both at the single motor and cargo level. To explore these mechanisms, we developed a three dimensional simulation of cargo transport along microtubules by teams of kinesin-1 motors. We accounted for cargo membrane fluidity by explicitly simulating the Brownian dynamics of motors on the cargo surface and considered both the load and ATP dependence of single motor functioning. Our simulations show that surface fluidity could lead to the reduction of negative mechanical interference between kinesins and enhanced load sharing thereby increasing the average duration of single motors on the filament. This, along with a cooperative increase in on-rates as more motors bind leads to enhanced collective processivity. At the cargo level, surface fluidity makes more motors available for binding, which can act synergistically with the above effects to further increase transport distances though this effect is significant only at low ATP or high motor density. Additionally, the fluid surface allows for the clustering of motors at a well defined location on the surface relative to the microtubule and the fluid-coupled motors can exert more collective force per motor against loads. Our work on understanding how teamwork arises in cargo-coupled motors allows us to connect single motor properties to overall transport, sheds new light on cellular processes, reconciles existing observations, encourages new experimental validation efforts and can also suggest new ways of improving the transport of artificial cargo powered by motor teams. |
format | Online Article Text |
id | pubmed-9212169 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-92121692022-06-22 Cargo surface fluidity can reduce inter-motor mechanical interference, promote load-sharing and enhance processivity in teams of molecular motors Sarpangala, Niranjan Gopinathan, Ajay PLoS Comput Biol Research Article In cells, multiple molecular motors work together as teams to carry cargoes such as vesicles and organelles over long distances to their destinations by stepping along a network of cytoskeletal filaments. How motors that typically mechanically interfere with each other, work together as teams is unclear. Here we explored the possibility that purely physical mechanisms, such as cargo surface fluidity, may potentially enhance teamwork, both at the single motor and cargo level. To explore these mechanisms, we developed a three dimensional simulation of cargo transport along microtubules by teams of kinesin-1 motors. We accounted for cargo membrane fluidity by explicitly simulating the Brownian dynamics of motors on the cargo surface and considered both the load and ATP dependence of single motor functioning. Our simulations show that surface fluidity could lead to the reduction of negative mechanical interference between kinesins and enhanced load sharing thereby increasing the average duration of single motors on the filament. This, along with a cooperative increase in on-rates as more motors bind leads to enhanced collective processivity. At the cargo level, surface fluidity makes more motors available for binding, which can act synergistically with the above effects to further increase transport distances though this effect is significant only at low ATP or high motor density. Additionally, the fluid surface allows for the clustering of motors at a well defined location on the surface relative to the microtubule and the fluid-coupled motors can exert more collective force per motor against loads. Our work on understanding how teamwork arises in cargo-coupled motors allows us to connect single motor properties to overall transport, sheds new light on cellular processes, reconciles existing observations, encourages new experimental validation efforts and can also suggest new ways of improving the transport of artificial cargo powered by motor teams. Public Library of Science 2022-06-08 /pmc/articles/PMC9212169/ /pubmed/35675381 http://dx.doi.org/10.1371/journal.pcbi.1010217 Text en © 2022 Sarpangala, Gopinathan https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Sarpangala, Niranjan Gopinathan, Ajay Cargo surface fluidity can reduce inter-motor mechanical interference, promote load-sharing and enhance processivity in teams of molecular motors |
title | Cargo surface fluidity can reduce inter-motor mechanical interference, promote load-sharing and enhance processivity in teams of molecular motors |
title_full | Cargo surface fluidity can reduce inter-motor mechanical interference, promote load-sharing and enhance processivity in teams of molecular motors |
title_fullStr | Cargo surface fluidity can reduce inter-motor mechanical interference, promote load-sharing and enhance processivity in teams of molecular motors |
title_full_unstemmed | Cargo surface fluidity can reduce inter-motor mechanical interference, promote load-sharing and enhance processivity in teams of molecular motors |
title_short | Cargo surface fluidity can reduce inter-motor mechanical interference, promote load-sharing and enhance processivity in teams of molecular motors |
title_sort | cargo surface fluidity can reduce inter-motor mechanical interference, promote load-sharing and enhance processivity in teams of molecular motors |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9212169/ https://www.ncbi.nlm.nih.gov/pubmed/35675381 http://dx.doi.org/10.1371/journal.pcbi.1010217 |
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