Skip to main content

High-throughput Measurements of Single Cell Rheology by Atomic Force Microscopy

  • Chapter
  • First Online:
Hyper Bio Assembler for 3D Cellular Systems

Abstract

The compliant mechanical properties of single cells have been extensively investigated and these properties are known to exhibit a strong dependence on the surrounding environments and also cell types, functions and conditions. An understanding of the cell behavior is important for applications of tissue engineering. Accurate rheological measurements are essential to elucidate the mechanisms of cell integrity and fluidity and are also key to mechanically identifying and separating single cells for cellular and tissue engineering. Of the various existing nano- and micro-rheology techniques, atomic force microscopy (AFM) shows great potential as a minimally invasive method. AFM allows mechanical measurements to be performed without the need for chemical modifications, via nano-scale contact between the AFM probe and the cell surface. In this chapter, we describe a recent advance in which micro-fabricated substrates are used for high-speed, automated AFM rheological measurements on size- and position-controlled cells.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Morris VJ, Kirby AR, Gunning AP (2009) Atomic force microscopy for biologists, 2nd edn. Imperial College Press, London

    Google Scholar 

  2. Guck J, Schinkinger S, Lincoln B, Wottawah F, Ebert S, Romeyke M, Lenz D, Erickson HM, Ananthakrishnan R, Mitchell D, Käs J, Ulvick S, Bilby C (2005) Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. Biophys J 88 (5):3689–3698

    Article  Google Scholar 

  3. Cross SE, Jin YS, Rao J, Gimzewski JK (2007) Nanomechanical analysis of cells from cancer patients. Nat Nanotechnol 2(12):780–783

    Article  Google Scholar 

  4. Plodinec M, Loparic M, Monnier CA, Obermann EC, Zanetti-Dallenbach R, Oertle P, Hyotyla JT, Aebi U, Bentires-Alj M, Lim RYH, Schoenenberger CA (2012) The nanomechanical signature of breast cancer. Nat Nanotechnol 7(11):757–765

    Article  Google Scholar 

  5. Gossett DR, Tse HT, Lee SA, Ying Y, Lindgren AG, Yang OO, Rao J, Clark AT, Di Carlo D (2012) Hydrodynamic stretching of single cells for large population mechanical phenotyping. Proc Natl Acad Sci U S A 109(20):7630–7635

    Article  Google Scholar 

  6. Singhvi R, Kumar A, Lopez G, Stephanopoulos G, Wang D, Whitesides G, Ingber D (1994) Engineering cell shape and function. Science 264:696–698.

    Article  Google Scholar 

  7. Kandere-Grzybowska K, Campbell C, Komarova Y, Grzybowski BA, Borisy GG (2005) Molecular dynamics imaging in micropatterned living cells. Nat Methods 2(10):739–741

    Article  Google Scholar 

  8. Hiratsuka S, Mizutani Y, Tsuchiya M, Kawahara K, Tokumoto H, Okajima T (2009) The number distribution of complex shear modulus of single cells measured by atomic force microscopy. Ultramicroscopy 109:937–941

    Article  Google Scholar 

  9. Cai P, Mizutani Y, Tsuchiya M, Maloney JM, Fabry B, Van Vliet KJ, Okajima T (2013) Quantifying cell-to-cell variation in power-law rheology. Biophys J 105(5):1093–1102

    Article  Google Scholar 

  10. Takahashi R, Ichikawa S, Subagyo A, Sueoka K, Okajima T (2014) Atomic force microscopy measurements of mechanical properties of single cells patterned by microcontact printing. Adv Robot 28:449–455

    Article  Google Scholar 

  11. Chen CS, Mrksich M, Huang S, Whitesides GM, Ingber DE (1997) Geometric control of cell life and death. Science 276(5317):1425–1428

    Article  Google Scholar 

  12. Théry M, Pépin A, Dressaire E, Chen Y, Bornens M (2006) Cell distribution of stress fibres in response to the geometry of the adhesive environment. Cell Motil Cytoskeleton 63(6):341–355

    Article  Google Scholar 

  13. Bhatia S, Yarmush M, Toner M (1997) Controlling cell interactions by micropatterning in co-cultures: hepatocytes and 3T3 fibroblasts. J Biomed Mater Res 34:189–199

    Article  Google Scholar 

  14. Kuribayashi K, Tsuda Y, Nakamura H, Takeuchi S (2010) Micro-patterning of phosphorylcholine-based polymers in a microfluidic channel. Sens Actuators B 149(1):177–183

    Article  Google Scholar 

  15. Tseng Q, Wang I, Duchemin-Pelletier E, Azioune A, Carpi N, Gao J, Filhol O, Piel M, Théry M, Balland M (2011) A new micropatterning method of soft substrates reveals that different tumorigenic signals can promote or reduce cell contraction levels. Lab Chip 11(13):2231–2240

    Article  Google Scholar 

  16. Carter S (1967) Haptotactic islands: a method of confining single cells to study individual cell reactions and clone formation. Exp Cell Res 48:189–193

    Article  Google Scholar 

  17. Selvarasah S, Chao S, Chen C, Sridhar S, Busnaina A, Khademhosseini A, Dokmecia M (2008) A reusable high aspect ratio parylene-C shadow mask technology for diverse micro-patterning applications. Sens Actuators A 145–146(1):306–315

    Article  Google Scholar 

  18. Folch A, Toner M (2000) Microengineering of cellular interactions. Annu Rev Biomed Eng 02:227–256

    Article  Google Scholar 

  19. Kuribayashi-Shigetomi K, Onoe H, Takeuchi S (2012) Cell origami: self-folding of three-dimensional cell-laden microstructures driven by cell traction force. PLoS One 7(12):e51085

    Article  Google Scholar 

  20. Teshima T, Onoe H, Kuribayashi-Shigetomi K, Aonuma H, Kamiya K, Ishihara H, Kanuka H, Takeuchi S (2014) Parylene mobile microplates integrated with an enzymatic release and handling of single adherent cells. Small 10(5):912–921

    Article  Google Scholar 

  21. Radmacher M, Tillmann RW, Fritz M, Gaub HE (1992) From molecules to cells – imaging soft samples with the atomic force microscope. Science 257(5078):1900–1905

    Article  Google Scholar 

  22. Radmacher M, Tilmann RW, Gaub HE (1993) Imaging viscoelasticity by force modulation with the atomic force microscope. Biophys J 64(3):735–742

    Article  Google Scholar 

  23. Alcaraz J, Buscemi L, Grabulosa M, Trepat X, Fabry B, Farre R, Navajas D (2003) Microrheology of Human lung epithelial cells measured by atomic force microscopy. Biophys J 84:2071–2079

    Article  Google Scholar 

  24. Mahaffy RE, Park S, Gerde E, Kas J, Shih CK (2004) Quantitative analysis of the viscoelastic properties of thin regions of fibroblasts using atomic force microscopy. Biophys J 86:1777–1793

    Article  Google Scholar 

  25. Ducker WA, Senden TJ, Pashley RM (1991) Direct measurement of colloidal forces using an atomic force microscope. Nature 353:239–241

    Article  Google Scholar 

  26. Landau LD, Lifshiz EM (1986) Theory of elasticity, 3rd edn. Pergamon Press, Oxford

    Google Scholar 

  27. Alcaraz J, Buscemi L, Puig-de-Morales M, Colchero J, Baro A, Navajas D (2002) Correction of microrheological measurements of soft samples with atomic force microscopy for the hydrodynamic drag on the cantilever. Langmuir 18:716–721

    Article  Google Scholar 

  28. Balland M, Desprat N, Icard D, Fereol S, Asnacios A, Browaeys J, Henon S, Gallet F (2006) Power laws in microrheology experiments on living cells: comparative analysis and modeling. Phys Rev E 74(2 Pt 1):021911

    Google Scholar 

  29. Massiera G, Van Citters KM, Biancaniello PL, Crocker JC (2007) Mechanics of single cells: rheology, time depndence, and fluctuations. Biophys J 93(10):3703–3713

    Article  Google Scholar 

  30. Desprat N, Richert A, Simeon J, Asnacios A (2005) Creep function of a single living cell. Biophys J 88(3):2224–2233

    Article  Google Scholar 

  31. Fabry B, Maksym GN, Butler JP, Glogauer M, Navajas D, Fredberg JJ (2001) Scaling the microrheology of living cells. Phys Rev Lett 87:148102

    Google Scholar 

  32. Fabry B, Maksym GN, Butler JP, Glogauer M, Navajas D, Taback NA, Millet EJ, Fredberg JJ (2003) Time scale and other invariants of integrative mechanical behavior in living cells. Phys Rev E 68:041914.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Takaharu Okajima .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Japan

About this chapter

Cite this chapter

Kuribayashi-Shigetomi, K., Takahashi, R., Subagyo, A., Sueoka, K., Okajima, T. (2015). High-throughput Measurements of Single Cell Rheology by Atomic Force Microscopy. In: Arai, T., Arai, F., Yamato, M. (eds) Hyper Bio Assembler for 3D Cellular Systems. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55297-0_4

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-55297-0_4

  • Published:

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-55296-3

  • Online ISBN: 978-4-431-55297-0

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics