Skip to main content
SpringerLink
Log in

Impulsive Enzymes: A New Force in Mechanobiology

  • Published:
Cellular and Molecular Bioengineering Aims and scope Submit manuscript

Abstract

We review studies that quantify newly discovered forces from single enzymatic reactions. These forces arise from the conversion of chemical energy to kinetic energy, which can be harnessed to direct diffusion of the enzyme up a concentration gradient of substrate, a novel phenomenon of molecular chemotaxis. When immobilized, enzymes can move fluid around them and perform directional pumping in microfluidic chambers. Because of the extensive array of enzymes in biological cells, we also develop three new hypotheses: that enzymatic self diffusion can assist in organizing signaling pathways in cells, can assist in pumping of fluid in cells, and can impose biologically significant forces on organelles, which will be manifested as stochastic motion not explained by thermal forces or myosin II. Such mechanochemical phenomena open up new directions in research in mechanobiology in which all enzymes, in addition to their primary function as catalysts for reactions, may have secondary functions as initiators of mechanosensitive transduction pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Beeg, J., et al. Transport of beads by several kinesin motors. Biophys. J. 94:532–541, 2008.

    Article  Google Scholar 

  2. Bursac, P., et al. Cytoskeletal remodelling and slow dynamics in the living cell. Nat. Mater. 4:557–561, 2005.

    Article  Google Scholar 

  3. Carrat, F., et al. Time lines of infection and disease in human influenza: a review of volunteer challenge studies. Am. J. Epidemiol. 167:775–785, 2008.

    Article  Google Scholar 

  4. Chance, B. The reaction of catalase and cyanide. J. Biol. Chem. 179:1299–1309, 1949.

    Google Scholar 

  5. Colberg, P. H., and R. Kapral. Ångström-scale chemically powered motors. EPL (Europhys. Lett.) 106:30004, 2014.

    Article  Google Scholar 

  6. Córdova-Figueroa, U. M., and J. F. Brady. Osmotic propulsion: the osmotic motor. Phys. Rev. Lett. 100:158303, 2008.

    Article  Google Scholar 

  7. Cressman, A., Y. Togashi, A. S. Mikhailov, and R. Kapral. Mesoscale modeling of molecular machines: cyclic dynamics and hydrodynamical fluctuations. Phys. Rev. E. Stat. Nonlinear Soft Matter Phys. 77:050901, 2008.

    Article  Google Scholar 

  8. Dangaria, J. H., and P. J. Butler. Macrorheology and adaptive microrheology of endothelial cells subjected to fluid shear stress. Am. J. Physiol. Cell Physiol. 293:C1568–C1575, 2007.

    Article  Google Scholar 

  9. Dey, K. K., S. Das, M. F. Poyton, S. Sengupta, P. J. Butler, P. S. Cremer, and A. Sen. Chemotactic separation of enzymes. ACS Nano 8:11941–11949, 2014.

  10. Elson, E. L., and D. Magde. Fluorescence correlation spectroscopy. I. Conceptual basis and theory. Biopolymers 13:1–27, 1974.

    Article  Google Scholar 

  11. Ermak, D. L., and J. A. McCammon. Brownian dynamics with hydrodynamic interactions. J. Chem. Phys. 69:1352, 1978.

    Article  Google Scholar 

  12. Goel, A., and V. Vogel. Harnessing biological motors to engineer systems for nanoscale transport and assembly. Nat. Nanotechnol. 3:465–475, 2008.

    Article  Google Scholar 

  13. Goldsmith, R. H., and W. E. Moerner. Watching conformational- and photo-dynamics of single fluorescent proteins in solution. Nat. Chem. 2:179–186, 2010.

    Article  Google Scholar 

  14. Goldstein, R. E., I. Tuval, and J.-W. van de Meent. Microfluidics of cytoplasmic streaming and its implications for intracellular transport. Proc. Natl. Acad. Sci. USA 105:3663–3667, 2008.

    Article  Google Scholar 

  15. Golestanian, R. Anomalous diffusion of symmetric and asymmetric active colloids. Phys. Rev. Lett. 102:188305, 2009.

    Article  Google Scholar 

  16. Golestanian, R. Synthetic mechanochemical molecular swimmer. Phys. Rev. Lett. 105:018103, 2010.

    Article  Google Scholar 

  17. Golestanian, R., and A. Ajdari. Mechanical response of a small swimmer driven by conformational transitions. Phys. Rev. Lett. 100:038101, 2008.

    Article  Google Scholar 

  18. Golestanian, R., T. Liverpool, and A. Ajdari. Propulsion of a molecular machine by asymmetric distribution of reaction products. Phys. Rev. Lett. 94:220801, 2005.

    Article  Google Scholar 

  19. Gullapalli, R. R., T. Tabouillot, R. Mathura, J. H. Dangaria, and P. J. Butler. Integrated multimodal microscopy, time-resolved fluorescence, and optical-trap rheometry: toward single molecule mechanobiology. J. Biomed. Opt. 12:14012, 2007.

    Article  Google Scholar 

  20. Guo, M., et al. Probing the stochastic, motor-driven properties of the cytoplasm using force spectrum microscopy. Cell 158:822–832, 2014.

    Article  Google Scholar 

  21. Hancock, W. O. Bidirectional cargo transport: moving beyond tug of war. Nat. Rev. Mol. Cell Biol. 15:615–628, 2014.

    Article  Google Scholar 

  22. Henzler-Wildman, K. A., et al. Intrinsic motions along an enzymatic reaction trajectory. Nature 450:838–844, 2007.

    Article  Google Scholar 

  23. Hoffman, B. D., G. Massiera, K. M. Van Citters, and J. C. Crocker. The consensus mechanics of cultured mammalian cells. Proc. Natl. Acad. Sci. USA 103:10259–10264, 2006.

    Article  Google Scholar 

  24. Hoffman, B. D., C. Grashoff, and M. A. Schwartz. Dynamic molecular processes mediate cellular mechanotransduction. Nature 475:316–323, 2011.

    Article  Google Scholar 

  25. Hong, Y., N. Blackman, N. Kopp, A. Sen, and D. Velegol. Chemotaxis of nonbiological colloidal rods. Phys. Rev. Lett. 99:178103, 2007.

    Article  Google Scholar 

  26. Hurt, A. C., et al. Performance of influenza rapid point-of-care tests in the detection of swine lineage A(H1N1) influenza viruses. Influenza Other Respir. Viruses 3:171–176, 2009.

    Article  Google Scholar 

  27. Ke, H., S. Ye, R. L. Carroll, and K. Showalter. Motion analysis of self-propelled Pt-silica particles in hydrogen peroxide solutions. J. Phys. Chem. A 114:5462–5467, 2010.

    Article  Google Scholar 

  28. Lee, S. E., R. D. Kamm, and M. R. Mofrad. Force-induced activation of talin and its possible role in focal adhesion mechanotransduction. J. Biomech. 40:2096–2106, 2007.

    Article  Google Scholar 

  29. Lee, T.-C., et al. Self-propelling nanomotors in the presence of strong Brownian forces. Nano Lett. 14:2407–2412, 2014.

    Article  Google Scholar 

  30. Liou, G.-Y., and P. Storz. Reactive oxygen species in cancer. Free Radic. Res. 44:479–496, 2010.

    Article  Google Scholar 

  31. Magde, D., E. L. Elson, and W. W. Webb. Fluorescence correlation spectroscopy. II. An experimental realization. Biopolymers 13:29–61, 1974.

    Article  Google Scholar 

  32. Mahadevan, L., and P. Matsudaira. Motility powered by supramolecular springs and ratchets. Science 288:95–100, 2000.

    Article  Google Scholar 

  33. Mehta, A. D., M. Rief, J. A. Spudich, D. A. Smith, and R. M. Simmons. Single-molecule biomechanics with optical methods. Science 283:1689–1695, 1999.

    Article  Google Scholar 

  34. Moscona, A. Neuraminidase inhibitors for influenza. N. Engl. J. Med. 353:1363–1373, 2005.

    Article  Google Scholar 

  35. Muddana, H. S., S. Sengupta, T. E. Mallouk, A. Sen, and P. J. Butler. Substrate catalysis enhances single-enzyme diffusion. J. Am. Chem. Soc. 132:2110–2111, 2010.

    Article  Google Scholar 

  36. Nordberg, J., and E. S. Arnér. Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic. Biol. Med. 31:1287–1312, 2001.

    Article  Google Scholar 

  37. Oiwa, K., and H. Sakakibara. Recent progress in dynein structure and mechanism. Curr. Opin. Cell Biol. 17:98–103, 2005.

    Article  Google Scholar 

  38. Parry, B. R., et al. The bacterial cytoplasm has glass-like properties and is fluidized by metabolic activity. Cell 156:183–194, 2014.

    Article  Google Scholar 

  39. Purcell, E. M. Life at low Reynolds number. Am. J. Phys. 45:3, 1977.

    Article  Google Scholar 

  40. Riedel, C., et al. The heat released during catalytic turnover enhances the diffusion of an enzyme. Nature 2014. doi:10.1038/nature14043.

    Google Scholar 

  41. Sakaue, T., R. Kapral, and A. S. Mikhailov. Nanoscale swimmers: hydrodynamic interactions and propulsion of molecular machines. Eur. Phys. J. B 75:381–387, 2010.

    Article  MATH  Google Scholar 

  42. Schliwa, M., and G. Woehlke. Molecular motors. Nature 422:759–765, 2003.

    Article  Google Scholar 

  43. Seger, R., and E. G. Krebs. The MAPK signaling cascade. FASEB J. 9:726–735, 1995.

    Google Scholar 

  44. Sengupta, S., et al. Enzyme molecules as nanomotors. J. Am. Chem. Soc. 135:1406–1414, 2013.

    Article  Google Scholar 

  45. Sengupta, S., et al. DNA polymerase as a molecular motor and pump. ACS Nano 8:2410–2418, 2014.

    Article  Google Scholar 

  46. Sengupta, S., et al. Self-powered enzyme micropumps. Nat. Chem. 6:415–422, 2014.

    Article  Google Scholar 

  47. Spudich, J. A., S. E. Rice, R. S. Rock, T. J. Purcell, and H. M. Warrick. Optical traps to study properties of molecular motors. Cold Spring Harb. Protoc. 2011:1305–1318, 2011.

    Google Scholar 

  48. Switala, J., and P. C. Loewen. Diversity of properties among catalases. Arch. Biochem. Biophys. 401:145–154, 2002.

    Article  Google Scholar 

  49. Tayo, A., J. Ellis, L. Linden Phillips, S. Simpson, and D. J. Ward. Emerging point of care tests for influenza: innovation or status quo. Influenza Other Respir. Viruses 6:291–298, 2012.

    Article  Google Scholar 

  50. Tian, A., and T. Baumgart. Sorting of lipids and proteins in membrane curvature gradients. Biophys. J. 96:2676–2688, 2009.

    Article  Google Scholar 

  51. Tian, T., et al. Plasma membrane nanoswitches generate high-fidelity Ras signal transduction. Nat. Cell Biol. 9:905–914, 2007.

    Article  Google Scholar 

  52. Tyska, M. J., and D. M. Warshaw. The myosin power stroke. Cell Motil. Cytoskelet. 51:1–15, 2002.

    Article  Google Scholar 

  53. Vale, R. D., and R. A. Milligan. The way things move: looking under the hood of molecular motor proteins. Science 288:88–95, 2000.

    Article  Google Scholar 

  54. Valentine, M., et al. Investigating the microenvironments of inhomogeneous soft materials with multiple particle tracking. Phys. Rev. E 64:061506, 2001.

    Article  Google Scholar 

  55. Wang, N., J. P. Butler, and D. E. Ingber. Mechanotransduction across the cell surface and through the cytoskeleton. Science 260:1124–1127, 1993.

    Article  Google Scholar 

  56. Yamada, S., D. Wirtz, and S. C. Kuo. Mechanics of living cells measured by laser tracking microrheology. Biophys. J. 78:1736–1747, 2000.

    Article  Google Scholar 

  57. Yin, H., et al. Transcription against an applied force. Science 270:1653–1657, 1995.

    Article  Google Scholar 

Download references

Acknowledgments

PJB acknowledges financial support from the National Science Foundation. CMMI-1334847. AS acknowledges financial support from the Penn State Center for Nanoscale Science (NSF-MRSEC, DMR-0820404).

Conflict of interest

Peter J. Butler, Krishna K. Dey, and Ayusman Sen have no conflicts of interest to declare.

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, The Pennsylvania State University, 205 Hallowell Building, University Park, PA, 16802, USA

    Peter J. Butler

  2. Department of Chemistry, The Pennsylvania State University, 104 Chemistry Building, University Park, PA, 16802, USA

    Krishna K. Dey & Ayusman Sen

Authors
  1. Peter J. Butler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Krishna K. Dey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ayusman Sen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Peter J. Butler or Ayusman Sen.

Additional information

Associate Editor Edward Sander oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Butler, P.J., Dey, K.K. & Sen, A. Impulsive Enzymes: A New Force in Mechanobiology. Cel. Mol. Bioeng. 8, 106–118 (2015). https://doi.org/10.1007/s12195-014-0376-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12195-014-0376-1

Keywords

Search

Navigation