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Force production by disassembling microtubules


Microtubules (MTs) are important components of the eukaryotic cytoskeleton: they contribute to cell shape and movement, as well as to the motions of organelles including mitotic chromosomes. MTs bind motor enzymes that drive many such movements, but MT dynamics can also contribute to organelle motility1,2,3,4,5,6,7,8. Each MT polymer is a store of chemical energy that can be used to do mechanical work, but how this energy is converted to motility remains unknown. Here we show, by conjugating glass microbeads to tubulin polymers through strong inert linkages, such as biotin–avidin, that depolymerizing MTs exert a brief tug on the beads, as measured with laser tweezers. Analysis of these interactions with a molecular-mechanical model of MT structure and force production9,10 shows that a single depolymerizing MT can generate about ten times the force that is developed by a motor enzyme; thus, this mechanism might be the primary driving force for chromosome motion. Because even the simple coupler used here slows MT disassembly, physiological couplers may modulate MT dynamics in vivo.

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Figure 1: Experimental design.
Figure 2: Example signals.
Figure 3: Analysis of force production.
Figure 4: Models of force production.


  1. Inoue, S. & Salmon, E. D. Force generation by microtubule assembly/disassembly in mitosis and related movements. Mol. Biol. Cell 6, 1619–1640 (1995)

    CAS  Article  Google Scholar 

  2. Dogterom, M., Kerssemakers, J. W., Romet-Lemonne, G. & Janson, M. E. Force generation by dynamic microtubules. Curr. Opin. Cell Biol. 17, 67–74 (2005)

    CAS  Article  Google Scholar 

  3. Waterman-Storer, C. M. & Salmon, E. D. Endoplasmic reticulum membrane tubules are distributed by microtubules in living cells using three distinct mechanisms. Curr. Biol. 8, 798–806 (1998)

    CAS  Article  Google Scholar 

  4. Waterman-Storer, C. M., Worthylake, R. A., Liu, B. P., Burridge, K. & Salmon, E. D. Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts. Nature Cell Biol. 1, 45–50 (1999)

    CAS  Article  Google Scholar 

  5. Koshland, D. E., Mitchison, T. J. & Kirschner, M. W. Polewards chromosome movement driven by microtubule depolymerization in vitro. Nature 331, 499–504 (1988)

    ADS  CAS  Article  Google Scholar 

  6. Coue, M., Lombillo, V. A. & McIntosh, J. R. Microtubule depolymerization promotes particle and chromosome movement in vitro. J. Cell Biol. 112, 1165–1175 (1991)

    CAS  Article  Google Scholar 

  7. Lombillo, V. A., Nislow, C., Yen, T. J., Gelfand, V. I. & McIntosh, J. R. Antibodies to the kinesin motor domain and CENP-E inhibit microtubule depolymerization-dependent motion of chromosomes in vitro. J. Cell Biol. 128, 107–115 (1995)

    CAS  Article  Google Scholar 

  8. Lombillo, V. A., Stewart, R. J. & McIntosh, J. R. Minus-end-directed motion of kinesin-coated microspheres driven by microtubule depolymerization. Nature 373, 161–164 (1995)

    ADS  CAS  Article  Google Scholar 

  9. Molodtsov, M. I. et al. A molecular-mechanical model of the microtubule. Biophys. J. 88, 3167–3179 (2005)

    ADS  CAS  Article  Google Scholar 

  10. Molodtsov, M. I., Grishchuk, E. L., Efremov, A. K., McIntosh, J. R. & Ataullakhanov, F. I. Force production by depolymerizing microtubules: a theoretical study. Proc. Natl Acad. Sci. USA 102, 4353–4358 (2005)

    ADS  CAS  Article  Google Scholar 

  11. Muller-Reichert, T., Chretien, D., Severin, F. & Hyman, A. A. Structural changes at microtubule ends accompanying GTP hydrolysis: information from a slowly hydrolyzable analogue of GTP, guanylyl (α,β)methylenediphosphonate. Proc. Natl Acad. Sci. USA 95, 3661–3666 (1998)

    ADS  CAS  Article  Google Scholar 

  12. Gigant, B. et al. The 4Å X-ray structure of a tubulin:stathmin-like domain complex. Cell 102, 809–816 (2000)

    CAS  Article  Google Scholar 

  13. Caplow, M., Ruhlen, R. L. & Shanks, J. The free energy for hydrolysis of a microtubule-bound nucleotide triphosphate is near zero: all of the free energy for hydrolysis is stored in the microtubule lattice. J. Cell Biol. 127, 779–788 (1994)

    CAS  Article  Google Scholar 

  14. Howard, J. & Hyman, A. A. Dynamics and mechanics of the microtubule plus end. Nature 422, 753–758 (2003)

    ADS  CAS  Article  Google Scholar 

  15. Mandelkow, E. M., Mandelkow, E. & Milligan, R. A. Microtubule dynamics and microtubule caps: a time-resolved cryo-electron microscopy study. J. Cell Biol. 114, 977–991 (1991)

    CAS  Article  Google Scholar 

  16. Hyman, A. A., Salser, S., Drechsel, D. N., Unwin, N. & Mitchison, T. J. Role of GTP hydrolysis in microtubule dynamics: information from a slowly hydrolyzable analogue, GMPCPP. Mol. Biol. Cell 3, 1155–1167 (1992)

    CAS  Article  Google Scholar 

  17. Vigers, G. P., Coue, M. & McIntosh, J. R. Fluorescent microtubules break up under illumination. J. Cell Biol. 107, 1011–1024 (1988)

    CAS  Article  Google Scholar 

  18. Allersma, M. W., Gittes, F., deCastro, M. J., Stewart, R. J. & Schmidt, C. F. Two-dimensional tracking of ncd motility by back focal plane interferometry. Biophys. J. 74, 1074–1085 (1998)

    ADS  CAS  Article  Google Scholar 

  19. Visscher, K. & Block, S. M. Versatile optical traps with feedback control. Methods Enzymol. 298, 460–489 (1998)

    CAS  Article  Google Scholar 

  20. Svoboda, K. & Block, S. M. Force and velocity measured for single kinesin molecules. Cell 77, 773–784 (1994)

    CAS  Article  Google Scholar 

  21. Westermann, S. et al. Formation of a dynamic kinetochore-microtubule interface through assembly of the Dam1 ring complex. Mol. Cell 17, 277–290 (2005)

    CAS  Article  Google Scholar 

  22. Gildersleeve, R. F., Cross, A. R., Cullen, K. E., Fagen, A. P. & Williams, R. C. Jr Microtubules grow and shorten at intrinsically variable rates. J. Biol. Chem. 267, 7995–8006 (1992)

    CAS  PubMed  Google Scholar 

  23. O'Brien, E. T., Salmon, E. D., Walker, R. A. & Erickson, H. P. Effects of magnesium on the dynamic instability of individual microtubules. Biochemistry 29, 6648–6656 (1990)

    CAS  Article  Google Scholar 

  24. Walker, R. A. et al. Dynamic instability of individual microtubules analyzed by video light microscopy: rate constants and transition frequencies. J. Cell Biol. 107, 1437–1448 (1988)

    CAS  Article  Google Scholar 

  25. Fygenson, D. K., Braun, E. & Libchaber, A. Phase diagram of microtubules. Phys. Rev. E 50, 1579–1588 (1994)

    ADS  CAS  Article  Google Scholar 

  26. Hunt, A. J. & McIntosh, J. R. The dynamic behaviour of individual microtubules associated with chromosomes in vitro. Mol. Biol. Cell 9, 249–261 (1998)

    Article  Google Scholar 

  27. Miranda, J. L., De Wulf, P., Sorger, P. & Harrison, S. C. The yeast DASH complex forms closed rings on microtubules. Nature Struct. Mol. Biol. 12, 138–143 (2005)

    CAS  Article  Google Scholar 

  28. Nicklas, R. B. How cells get the right chromosomes. Science 275, 632–637 (1997)

    CAS  Article  Google Scholar 

  29. McIntosh, J. R., Grishchuk, E. L. & West, R. R. Chromosome–microtubule interactions during mitosis. Annu. Rev. Cell. Dev. Biol. 18, 193–219 (2002)

    CAS  Article  Google Scholar 

  30. Brouhard, G. J., Schek, H. T. III & Hunt, A. J. Advanced optical tweezers for the study of cellular and molecular biomechanics. IEEE Trans. Biomed. Eng. 50, 121–125 (2003)

    Article  Google Scholar 

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We thank A. Hunt and G. J. Bouchard for sharing the plans for their laser tweezers; T. Perkins for advice, the quadrant photo detector design and programs to help with instrument calibration; H. Higuchi for tips on buffers; and members of McIntosh laboratory, and A. I. Vorobjev and G. P. Georgiev for help and support. V. Sarbash, T. Buxkemper and C. Bowen helped with building the trap. This work was supported in part by grants from the NIH to J.R.M., who is a Research Professor of the American Cancer Society.

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Correspondence to J. Richard McIntosh.

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Supplementary information

Supplementary Notes

This file contains a description of our mathematical model of MT depolymerization, of MT-bead association, and of the laser trap. We calculate the position of the bead and shape of the MT when depolymerization is triggered via two scenarios described in the article. These calculations are compared with experimental results. The last section presents equations that were used to fit the experimental curves (DOC 43 kb)

Supplementary Figures

This file contains Supplementary Figures 1–3 and their legends. The figures display calculated profiles of the bead-MT system and the corresponding graphs. (PDF 499 kb)

Supplementary Video

Each frame shows the result of a calculation of the MT-bead configuration for “depolymerization” of one dimer layer via scenario 1. The bead moves when bending occurs in the bead–associated dimers and the dimers immediately downstream from it. All parameters are as in Supplementary Figure 2, except the attached dimers are # 10–14. The initial configuration is shown in gray. (MOV 132 kb)

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Grishchuk, E., Molodtsov, M., Ataullakhanov, F. et al. Force production by disassembling microtubules. Nature 438, 384–388 (2005).

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