Analysis of Cooperative Behavior in Multiple Kinesins Motor Protein Transport by Varying Structural and Chemical Properties


Intracellular transport is a fundamental biological process during which cellular materials are driven by enzymatic molecules called motor proteins. Recent optical trapping experiments and theoretical analysis have uncovered many features of cargo transport by multiple kinesin motor protein molecules under applied loads. These studies suggest that kinesins cooperate negatively under typical transport conditions, although some productive cooperation could be achieved under higher applied loads. However, the microscopic origins of this complex behavior are still not well understood. Using a discrete-state stochastic approach we analyze factors that affect the cooperativity among kinesin motors during cargo transport. Kinesin cooperation is shown to be largely unaffected by the structural and mechanical parameters of a multiple motor complex connected to a cargo, but much more sensitive to biochemical parameters affecting motor–filament affinities. While such behavior suggests the net negative cooperative responses of kinesins will persist across a relatively wide range of cargo types, it is also shown that the rates with which cargo velocities relax in time upon force perturbations are influenced by structural factors that affect the free energies of and load distributions within a multiple kinesin complex. The implications of these later results on transport phenomena where loads change temporally, as in the case of bidirectional transport, are discussed.

This is a preview of subscription content, access via your institution.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5


  1. 1.

    Alberts, B., et al. Molecular Biology of the Cell (4th ed.). USA: Taylor & Francis, 2002.

    Google Scholar 

  2. 2.

    Ali, Y. M., G. G. Kennedy, D. Safer, K. M. Trybus, L. H. Sweeney, and D. M. Warshaw. Myosin Va and myosin VI coordinate their steps while engaged in an in vitro tug of war during cargo transport. Proc. Natl. Acad. Sci. U.S.A. 108:E535–E541, 2011.

    Article  Google Scholar 

  3. 3.

    Ali, Y. M., H. Lu, C. S. Bookwalter, D. M. Warshaw, and K. M. Trybus. Myosin V and Kinesin act as tethers to enhance each others’ processivity. Proc. Natl. Acad. Sci. U.S.A. 105:4691–4696, 2008.

    Article  Google Scholar 

  4. 4.

    Ally, S., A. G. Larson, K. Barlan, S. E. Rice, and V. I. J. Gelfand. Opposite-polarity motors activate one another to trigger cargo transport in live cells. Cell Biol. 187:1071–1082, 2009.

    Article  Google Scholar 

  5. 5.

    Campas, O., Y. Kafri, K. B. Zeldovich, J. Casademunt, and J.-F. Joanny. Collective dynamics of interacting molecular motors. Phys. Rev. Lett. 97:038101, 2006.

    Article  Google Scholar 

  6. 6.

    Driver, J. W., K. D. Jamison, K. Uppulury, A. R. Rogers, A. B. Kolomeisky, and M. R. Diehl. Productive cooperation among processive motors depends inversely on their mechanochemical efficiency. Biophys. J . 101:386–395, 2011.

    Article  Google Scholar 

  7. 7.

    Driver, J. W., A. R. Rogers, K. D. Jamison, R. K. Das, A. B. Kolomeisky, and M. R. Diehl. Coupling between motor proteins determines dynamic behaviors of motor protein assemblies. Phys. Chem. Chem. Phys. 12:10398–10405, 2010.

    Article  Google Scholar 

  8. 8.

    Holzbaur, E. L. F., and Y. E. Goldman. Coordination of molecular motors: from in vitro assays to intracellular dynamics. Curr. Opin. Cell Biol. 22:4–13, 2010.

    Article  Google Scholar 

  9. 9.

    Howard, J. Mechanics of motor proteins and the cytoskeleton. Sunderland, MA: Sinauer Associates, 2001.

    Google Scholar 

  10. 10.

    Jamison, K. D., J. W. Driver, and M. R. J. Diehl. Cooperative responses of multiple kinesins to variable and constant loads. Biol. Chem. 287:3357–3365, 2012.

    Article  Google Scholar 

  11. 11.

    Jamison, K. D., J. W. Driver, A. R. Rogers, P. E. Constantinou, and M. R. Diehl. Two kinesins transport cargo primarily via the action of one motor: implications for intracellular transport. Biophys. J . 99:2967–2977, 2010.

    Article  Google Scholar 

  12. 12.

    Klumpp, S., and R. Lipowsky. Cooperative cargo transport by several molecular motors. Proc. Natl. Acad. Sci. U.S.A. 102:17284–17289, 2005.

    Article  Google Scholar 

  13. 13.

    Kulić, I. M., A. E. X. Brown, H. Kim, C. Kural, B. Blehm, P. R. Selvin, P. C. Nelson, and V. I. Gelfand. The role of microtubule movement in bidirectional organelle transport. Proc. Natl. Acad. Sci. U.S.A. 105:10011–10016, 2008.

    Article  Google Scholar 

  14. 14.

    Kunwar, A., and A. Mogilner. Robust transport by multiple motors with nonlinear force-velocity relations and stochastic load sharing. Phys. Biol. 7:016012, 2010.

    Article  Google Scholar 

  15. 15.

    Kural, C., H. Kim, S. Syed, G. Goshima, V. I. Gelfand, and P. R. Selvin. Kinesin and dynein move a peroxisome in vivo: a tug-of-war or coordinated movement? Science 308:1469–1472, 2005.

    Article  Google Scholar 

  16. 16.

    Laib, J. A., J. A. Marin, R. A. Bloodgood, and W. H. Guilford. The reciprocal coordination and mechanics of molecular motors in living cells. Proc. Natl. Acad. Sci. U.S.A. 106:3190–3195, 2009.

    Article  Google Scholar 

  17. 17.

    Leduc, C., O. Campas, K. B. Zeldovich, A. Roux, P. Jolimaitre, L. Bourel-Bonnet, B. Goud, J.-F. Joanny, P. Bassereau, and J. Prost. Cooperative extraction of membrane nanotubes by molecular motors. Proc. Natl. Acad. Sci. U.S.A. 101:17096–17101, 2004.

    Google Scholar 

  18. 18.

    Leduc, C., N. Pavin, F. Julicher, and S. Diez. Collective behavior of antagonistically acting kinesin-1 motors. Phys. Rev. Lett. 105:128103, 2010.

    Article  Google Scholar 

  19. 19.

    Leduc, C., F. Ruhnow, J. Howard, and S. Diez. Detection of fractional steps in cargo movement by the collective operation of kinesin-1 motors. Proc. Natl. Acad. Sci. U.S.A. 104:10847–10852, 2007.

    Article  Google Scholar 

  20. 20.

    Lu, H., A. K. Efremov, C. S. Bookwalter, E. B. Krementsova, J. W. Driver, K. M. Trybus, and M. R. Diehl. Collective dynamics of elastically coupled myosin V motors. J. Biol. Chem. 287(33):27753–27761, 2012.

    Article  Google Scholar 

  21. 21.

    Muller, M. J. I., S. Klumpp, and R. Lipowsky. Tug-of-war as a cooperative mechanism for bidirectional cargo transport by molecular motors. Proc. Natl. Acad. Sci. U.S.A. 105:4609–4614, 2008.

    Article  Google Scholar 

  22. 22.

    Ou, G. S., O. E. Blacque, J. J. Snow, M. R. Leroux, and J. M. Scholey. Functional coordination of intraflagellar transport motors. Nature 436:583–587, 2005.

    Article  Google Scholar 

  23. 23.

    Rogers, A. R., J. W. Driver, P. E. Constantinou, K. D. Jamison, and M. R. Diehl. Negative interference dominates collective transport of kinesin motors in the absence of load. Phys. Chem. Chem. Phys. 11:4882–4889, 2009.

    Article  Google Scholar 

  24. 24.

    Rogers, S. L., I. S. Tint, P. C. Fanapour, and V. I. Gelfand. Regulated bidirectional motility of melanophore pigment granules along microtubules in vitro. Proc. Natl. Acad. Sci. U.S.A. 94:3720–3725, 1997.

    Article  Google Scholar 

  25. 25.

    Ross, J. L., K. Wallace, H. Shuman, Y. E. Goldman, and E. L. F. Holzbaur. Processive bidirectional motion of dynein–dynactin complexes in vitro. Nat. Cell Biol. 8:562–570, 2006.

    Article  Google Scholar 

  26. 26.

    Uppulury, K., A. K. Efremov, J. W. Driver, D. K. Jamison, M. R. Diehl, and A. B. J. Kolomeisky. How the interplay between mechanical and nonmechanical interactions affects multiple kinesin dynamics. Phys. Chem. B 116:8846–8855, 2012.

    Article  Google Scholar 

  27. 27.

    Vale, R. D. The molecular motor toolbox for intracellular transport. Cell 112:467–480, 2003.

    Article  Google Scholar 

  28. 28.

    Xu, J., Z. Shu, S. J. King, and S. P. Gross. Tuning multiple motor travel via single motor velocity. Traffic 13:1198–1205, 2012.

    Article  Google Scholar 

Download references


This work was supported by grants from the National Science Foundation (MCB-0643832), the National Institute of Health (1R01GM094489-01) and the Welch Foundation (C-1559 to A.B.K. and C-1625 to M.R.D.).

Author information



Corresponding author

Correspondence to Anatoly B. Kolomeisky.

Additional information

Associate Editor Jung-Chi Liao & Henry Hess oversaw the review of this article.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Uppulury, K., Efremov, A.K., Driver, J.W. et al. Analysis of Cooperative Behavior in Multiple Kinesins Motor Protein Transport by Varying Structural and Chemical Properties. Cel. Mol. Bioeng. 6, 38–47 (2013).

Download citation


  • Intracellular transport
  • Kinesin
  • Cooperativity