Mechanical stochastic tug-of-war models cannot explain bidirectional lipid-droplet transport

Ambarish Kunwar, Suvranta K. Tripathy, Jing Xu, Michelle K. Mattson, Preetha Anand, Roby Sigua, Michael Vershinin, Richard J. McKenney, Clare C. Yu, Alexander Mogilner, Steven P. Gross

Research output: Contribution to journalArticle

Abstract

Intracellular transport via the microtubule motors kinesin and dynein plays an important role in maintaining cell structure and function. Often, multiple kinesin or dynein motors move the same cargo. Their collective function depends critically on the single motors' detachment kinetics under load, which we experimentally measure here. This experimental constraint - combined with other experimentally determined parameters - is then incorporated into theoretical stochastic and mean-field models. Comparison of modeling results and in vitro data shows good agreement for the stochastic, but not mean-field, model. Many cargos in vivo move bidirectionally, frequently reversing course. Because both kinesin and dynein are present on the cargos, one popular hypothesis explaining the frequent reversals is that the opposite-polarity motors engage in unregulated stochastic tugs-of-war. Then, the cargos'motion can be explained entirely by the outcome of these opposite- motor competitions. Here, we use fully calibrated stochastic and mean-field models to test the tug-of-war hypothesis. Neither model agrees well with our in vivo data, suggesting that, in addition to inevitable tugs-of-war between opposite motors, there is an additional level of regulation not included in the models.

Original languageEnglish (US)
Pages (from-to)18960-18965
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number47
DOIs
StatePublished - Nov 22 2011

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Dyneins
Kinesin
Microtubules
Warfare
Lipid Droplets

ASJC Scopus subject areas

  • General

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Mechanical stochastic tug-of-war models cannot explain bidirectional lipid-droplet transport. / Kunwar, Ambarish; Tripathy, Suvranta K.; Xu, Jing; Mattson, Michelle K.; Anand, Preetha; Sigua, Roby; Vershinin, Michael; McKenney, Richard J.; Yu, Clare C.; Mogilner, Alexander; Gross, Steven P.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 47, 22.11.2011, p. 18960-18965.

Research output: Contribution to journalArticle

Kunwar, A, Tripathy, SK, Xu, J, Mattson, MK, Anand, P, Sigua, R, Vershinin, M, McKenney, RJ, Yu, CC, Mogilner, A & Gross, SP 2011, 'Mechanical stochastic tug-of-war models cannot explain bidirectional lipid-droplet transport', Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 47, pp. 18960-18965. https://doi.org/10.1073/pnas.1107841108
Kunwar, Ambarish ; Tripathy, Suvranta K. ; Xu, Jing ; Mattson, Michelle K. ; Anand, Preetha ; Sigua, Roby ; Vershinin, Michael ; McKenney, Richard J. ; Yu, Clare C. ; Mogilner, Alexander ; Gross, Steven P. / Mechanical stochastic tug-of-war models cannot explain bidirectional lipid-droplet transport. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 47. pp. 18960-18965.
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