Skip to main content
PMC home page
Biophysical Journal logoLink to Biophysical Journal
. 2002 Jun;82(6):3314–3329. doi: 10.1016/S0006-3495(02)75672-5

Magnetic tweezers: micromanipulation and force measurement at the molecular level.

Charlie Gosse 1, Vincent Croquette 1
PMCID: PMC1302119  PMID: 12023254

Abstract

Cantilevers and optical tweezers are widely used for micromanipulating cells or biomolecules for measuring their mechanical properties. However, they do not allow easy rotary motion and can sometimes damage the handled material. We present here a system of magnetic tweezers that overcomes those drawbacks while retaining most of the previous dynamometers properties. Electromagnets are coupled to a microscope-based particle tracking system through a digital feedback loop. Magnetic beads are first trapped in a potential well of stiffness approximately 10(-7) N/m. Thus, they can be manipulated in three dimensions at a speed of approximately 10 microm/s and rotated along the optical axis at a frequency of 10 Hz. In addition, our apparatus can work as a dynamometer relying on either usual calibration against the viscous drag or complete calibration using Brownian fluctuations. By stretching a DNA molecule between a magnetic particle and a glass surface, we applied and measured vertical forces ranging from 50 fN to 20 pN. Similarly, nearly horizontal forces up to 5 pN were obtained. From those experiments, we conclude that magnetic tweezers represent a low-cost and biocompatible setup that could become a suitable alternative to the other available micromanipulators.

Full Text

The Full Text of this article is available as a PDF (441.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allemand J. F., Bensimon D., Lavery R., Croquette V. Stretched and overwound DNA forms a Pauling-like structure with exposed bases. Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14152–14157. doi: 10.1073/pnas.95.24.14152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Amblard F, Maggs AC, Yurke B, Pargellis A, Leibler S. Subdiffusion and Anomalous Local Viscoelasticity in Actin Networks. Phys Rev Lett. 1996 Nov 18;77(21):4470–4473. doi: 10.1103/PhysRevLett.77.4470. [DOI] [PubMed] [Google Scholar]
  3. Ashkin A., Dziedzic J. M. Optical trapping and manipulation of viruses and bacteria. Science. 1987 Mar 20;235(4795):1517–1520. doi: 10.1126/science.3547653. [DOI] [PubMed] [Google Scholar]
  4. Bensimon D. Force: a new structural control parameter? Structure. 1996 Aug 15;4(8):885–889. doi: 10.1016/s0969-2126(96)00095-0. [DOI] [PubMed] [Google Scholar]
  5. Block S. M., Goldstein L. S., Schnapp B. J. Bead movement by single kinesin molecules studied with optical tweezers. Nature. 1990 Nov 22;348(6299):348–352. doi: 10.1038/348348a0. [DOI] [PubMed] [Google Scholar]
  6. Bouchiat C., Wang M. D., Allemand J., Strick T., Block S. M., Croquette V. Estimating the persistence length of a worm-like chain molecule from force-extension measurements. Biophys J. 1999 Jan;76(1 Pt 1):409–413. doi: 10.1016/s0006-3495(99)77207-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bustamante C., Macosko J. C., Wuite G. J. Grabbing the cat by the tail: manipulating molecules one by one. Nat Rev Mol Cell Biol. 2000 Nov;1(2):130–136. doi: 10.1038/35040072. [DOI] [PubMed] [Google Scholar]
  8. Cluzel P., Lebrun A., Heller C., Lavery R., Viovy J. L., Chatenay D., Caron F. DNA: an extensible molecule. Science. 1996 Feb 9;271(5250):792–794. doi: 10.1126/science.271.5250.792. [DOI] [PubMed] [Google Scholar]
  9. Evans E., Ritchie K. Dynamic strength of molecular adhesion bonds. Biophys J. 1997 Apr;72(4):1541–1555. doi: 10.1016/S0006-3495(97)78802-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Finer J. T., Simmons R. M., Spudich J. A. Single myosin molecule mechanics: piconewton forces and nanometre steps. Nature. 1994 Mar 10;368(6467):113–119. doi: 10.1038/368113a0. [DOI] [PubMed] [Google Scholar]
  11. Florin E. L., Moy V. T., Gaub H. E. Adhesion forces between individual ligand-receptor pairs. Science. 1994 Apr 15;264(5157):415–417. doi: 10.1126/science.8153628. [DOI] [PubMed] [Google Scholar]
  12. Gelles J., Schnapp B. J., Sheetz M. P. Tracking kinesin-driven movements with nanometre-scale precision. Nature. 1988 Feb 4;331(6155):450–453. doi: 10.1038/331450a0. [DOI] [PubMed] [Google Scholar]
  13. Gittes F., Schmidt C. F. Signals and noise in micromechanical measurements. Methods Cell Biol. 1998;55:129–156. doi: 10.1016/s0091-679x(08)60406-9. [DOI] [PubMed] [Google Scholar]
  14. Guilford W. H., Lantz R. C., Gore R. W. Locomotive forces produced by single leukocytes in vivo and in vitro. Am J Physiol. 1995 May;268(5 Pt 1):C1308–C1312. doi: 10.1152/ajpcell.1995.268.5.C1308. [DOI] [PubMed] [Google Scholar]
  15. Harada Y., Ohara O., Takatsuki A., Itoh H., Shimamoto N., Kinosita K., Jr Direct observation of DNA rotation during transcription by Escherichia coli RNA polymerase. Nature. 2001 Jan 4;409(6816):113–115. doi: 10.1038/35051126. [DOI] [PubMed] [Google Scholar]
  16. Heinrich V., Waugh R. E. A piconewton force transducer and its application to measurement of the bending stiffness of phospholipid membranes. Ann Biomed Eng. 1996 Sep-Oct;24(5):595–605. doi: 10.1007/BF02684228. [DOI] [PubMed] [Google Scholar]
  17. Ishijima A., Doi T., Sakurada K., Yanagida T. Sub-piconewton force fluctuations of actomyosin in vitro. Nature. 1991 Jul 25;352(6333):301–306. doi: 10.1038/352301a0. [DOI] [PubMed] [Google Scholar]
  18. Kellermayer M. S., Smith S. B., Granzier H. L., Bustamante C. Folding-unfolding transitions in single titin molecules characterized with laser tweezers. Science. 1997 May 16;276(5315):1112–1116. doi: 10.1126/science.276.5315.1112. [DOI] [PubMed] [Google Scholar]
  19. Kishino A., Yanagida T. Force measurements by micromanipulation of a single actin filament by glass needles. Nature. 1988 Jul 7;334(6177):74–76. doi: 10.1038/334074a0. [DOI] [PubMed] [Google Scholar]
  20. Liu Y., Sonek G. J., Berns M. W., Tromberg B. J. Physiological monitoring of optically trapped cells: assessing the effects of confinement by 1064-nm laser tweezers using microfluorometry. Biophys J. 1996 Oct;71(4):2158–2167. doi: 10.1016/S0006-3495(96)79417-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Maier B., Bensimon D., Croquette V. Replication by a single DNA polymerase of a stretched single-stranded DNA. Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12002–12007. doi: 10.1073/pnas.97.22.12002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Merkel R., Nassoy P., Leung A., Ritchie K., Evans E. Energy landscapes of receptor-ligand bonds explored with dynamic force spectroscopy. Nature. 1999 Jan 7;397(6714):50–53. doi: 10.1038/16219. [DOI] [PubMed] [Google Scholar]
  23. Moy V. T., Florin E. L., Gaub H. E. Intermolecular forces and energies between ligands and receptors. Science. 1994 Oct 14;266(5183):257–259. doi: 10.1126/science.7939660. [DOI] [PubMed] [Google Scholar]
  24. Neuman K. C., Chadd E. H., Liou G. F., Bergman K., Block S. M. Characterization of photodamage to Escherichia coli in optical traps. Biophys J. 1999 Nov;77(5):2856–2863. doi: 10.1016/S0006-3495(99)77117-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Noji H., Yasuda R., Yoshida M., Kinosita K., Jr Direct observation of the rotation of F1-ATPase. Nature. 1997 Mar 20;386(6622):299–302. doi: 10.1038/386299a0. [DOI] [PubMed] [Google Scholar]
  26. Paterson L., MacDonald M. P., Arlt J., Sibbett W., Bryant P. E., Dholakia K. Controlled rotation of optically trapped microscopic particles. Science. 2001 May 4;292(5518):912–914. doi: 10.1126/science.1058591. [DOI] [PubMed] [Google Scholar]
  27. Ryu W. S., Berry R. M., Berg H. C. Torque-generating units of the flagellar motor of Escherichia coli have a high duty ratio. Nature. 2000 Jan 27;403(6768):444–447. doi: 10.1038/35000233. [DOI] [PubMed] [Google Scholar]
  28. Sato M., Wong T. Z., Brown D. T., Allen R. D. Rheological properties of living cytoplasm: a preliminary investigation of squid axoplasm (Loligo pealei). Cell Motil. 1984;4(1):7–23. doi: 10.1002/cm.970040103. [DOI] [PubMed] [Google Scholar]
  29. Schnitzer M. J., Block S. M. Kinesin hydrolyses one ATP per 8-nm step. Nature. 1997 Jul 24;388(6640):386–390. doi: 10.1038/41111. [DOI] [PubMed] [Google Scholar]
  30. Simmons R. M., Finer J. T., Chu S., Spudich J. A. Quantitative measurements of force and displacement using an optical trap. Biophys J. 1996 Apr;70(4):1813–1822. doi: 10.1016/S0006-3495(96)79746-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Simson D. A., Ziemann F., Strigl M., Merkel R. Micropipet-based pico force transducer: in depth analysis and experimental verification. Biophys J. 1998 Apr;74(4):2080–2088. doi: 10.1016/S0006-3495(98)77915-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Strick T. R., Allemand J. F., Bensimon D., Bensimon A., Croquette V. The elasticity of a single supercoiled DNA molecule. Science. 1996 Mar 29;271(5257):1835–1837. doi: 10.1126/science.271.5257.1835. [DOI] [PubMed] [Google Scholar]
  33. Strick T. R., Allemand J. F., Bensimon D., Croquette V. Behavior of supercoiled DNA. Biophys J. 1998 Apr;74(4):2016–2028. doi: 10.1016/S0006-3495(98)77908-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Strick T. R., Croquette V., Bensimon D. Single-molecule analysis of DNA uncoiling by a type II topoisomerase. Nature. 2000 Apr 20;404(6780):901–904. doi: 10.1038/35009144. [DOI] [PubMed] [Google Scholar]
  35. Svoboda K., Block S. M. Biological applications of optical forces. Annu Rev Biophys Biomol Struct. 1994;23:247–285. doi: 10.1146/annurev.bb.23.060194.001335. [DOI] [PubMed] [Google Scholar]
  36. Wang N., Butler J. P., Ingber D. E. Mechanotransduction across the cell surface and through the cytoskeleton. Science. 1993 May 21;260(5111):1124–1127. doi: 10.1126/science.7684161. [DOI] [PubMed] [Google Scholar]
  37. Wuite G. J., Davenport R. J., Rappaport A., Bustamante C. An integrated laser trap/flow control video microscope for the study of single biomolecules. Biophys J. 2000 Aug;79(2):1155–1167. doi: 10.1016/S0006-3495(00)76369-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wuite G. J., Smith S. B., Young M., Keller D., Bustamante C. Single-molecule studies of the effect of template tension on T7 DNA polymerase activity. Nature. 2000 Mar 2;404(6773):103–106. doi: 10.1038/35003614. [DOI] [PubMed] [Google Scholar]
  39. YAGI K. The mechanical and colloidal properties of Amoeba protoplasm and their relations to the mechanism of amoeboid movement. Comp Biochem Physiol. 1961 Aug;3:73–91. doi: 10.1016/0010-406x(61)90134-7. [DOI] [PubMed] [Google Scholar]
  40. Yin H., Wang M. D., Svoboda K., Landick R., Block S. M., Gelles J. Transcription against an applied force. Science. 1995 Dec 8;270(5242):1653–1657. doi: 10.1126/science.270.5242.1653. [DOI] [PubMed] [Google Scholar]
  41. Zaner K. S., Valberg P. A. Viscoelasticity of F-actin measured with magnetic microparticles. J Cell Biol. 1989 Nov;109(5):2233–2243. doi: 10.1083/jcb.109.5.2233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Ziemann F., Rädler J., Sackmann E. Local measurements of viscoelastic moduli of entangled actin networks using an oscillating magnetic bead micro-rheometer. Biophys J. 1994 Jun;66(6):2210–2216. doi: 10.1016/S0006-3495(94)81017-3. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES