Skip to main content
SpringerLink
Log in

Use of the Quartz Crystal Microbalance with Dissipation Monitoring for Pharmacological Evaluation of Cell Signaling Pathways Mediated by Epidermal Growth Factor Receptors

  • Protocol
Label-Free Biosensor Methods in Drug Discovery

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

  • 1260 Accesses

Abstract

The quartz crystal microbalance with dissipation monitoring (QCM-D) is a highly sensitive, noninvasive, and label-free sensing device. This device is capable of providing real-time monitoring of the properties of complex biological systems, such as cells, in response to environmental stimuli. The unique dissipation monitoring function of the QCM-D has been shown to be able to profile the inhibition of signaling pathways mediated by epidermal growth factor receptors. The QCM-D method has the potential to become an effective sensing platform for drug screening.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
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 139.00
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. Carpenter G (1987) Receptors for epidermal growth factor and other polypeptide mitogens. Annu Rev Biochem 56(1):881–914. doi:10.1146/annurev.bi.56.070187.004313

    Article  CAS  PubMed  Google Scholar 

  2. Lemmon MA, Schlessinger J (2010) Cell signaling by receptor tyrosine kinases. Cell 141(7):1117–1134. doi:10.1016/j.cell.2010.06.011

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Scaltriti M, Baselga J (2006) The epidermal growth factor receptor pathway: a model for targeted therapy. Clin Cancer Res 12(18):5268–5272. doi:10.1158/1078-0432.ccr-05-1554

    Article  CAS  PubMed  Google Scholar 

  4. Osaki M, Oshimura M, Ito H (2004) PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis 9(6):667–676. doi:10.1023/B:APPT.0000045801.15585.dd

    Article  CAS  PubMed  Google Scholar 

  5. Xie W, Peng H, Zalkow LH, Li Y-H, Zhu C, Powis G, Kunkel M (2000) 3β-Hydroxy-6-aza-cholestane and related analogues as phosphatidylinositol specific phospholipase C (PI-PLC) inhibitors with antitumor activity. Bioorg Med Chem 8(4):699–706. doi:10.1016/S0968-0896(00)00014-6

    Article  CAS  PubMed  Google Scholar 

  6. Zandi R, Larsen AB, Andersen P, Stockhausen M-T, Poulsen HS (2007) Mechanisms for oncogenic activation of the epidermal growth factor receptor. Cell Signal 19(10):2013–2023. doi:10.1016/j.cellsig.2007.06.023

    Article  CAS  PubMed  Google Scholar 

  7. Sebastian S, Settleman J, Reshkin SJ, Azzariti A, Bellizzi A, Paradiso A (2006) The complexity of targeting EGFR signalling in cancer: from expression to turnover. Biochim Biophys Acta 1766(1):120–139. doi:10.1016/j.bbcan.2006.06.001

    CAS  PubMed  Google Scholar 

  8. Murphy-Ullrich JE (2001) The de-adhesive activity of matricellular proteins: is intermediate cell adhesion an adaptive state. J Clin Invest 107(7):785–790

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Welsh JB, Gill GN, Rosenfeld MG, Wells A (1991) A negative feedback loop attenuates EGF-induced morphological changes. J Cell Biol  114(3):533–543.  doi:10.1083/jcb.114.3.533

    Article  CAS  PubMed  Google Scholar 

  10. Xie H, Pallero MA, Gupta K, Chang P, Ware MF, Witke W, Kwiatkowski DJ, Lauffenburger DA, Murphy-Ullrich JE, Wells A (1998) EGF receptor regulation of cell motility: EGF induces disassembly of focal adhesions independently of the motility-associated PLCgamma signaling pathway. J Cell Sci 111(5):615–624

    CAS  PubMed  Google Scholar 

  11. Lauffenburger DA, Horwitz AF (1996) Cell migration: a physically integrated molecular process. Cell 84(3):359–369. doi:10.1016/S0092-8674(00)81280-5

    Article  CAS  PubMed  Google Scholar 

  12. Reginato MJ, Mills KR, Paulus JK, Lynch DK, Sgroi DC, Debnath J, Muthuswamy SK, Brugge JS (2003) Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis. Nat Cell Biol 5(8):733–740. doi:10.1038/ncb1026

    Article  CAS  PubMed  Google Scholar 

  13. Dei Tos AP, Ellis I (2005) Assessing epidermal growth factor receptor expression in tumours: what is the value of current test methods. Eur J Cancer 41(10):1383–1392. doi:10.1016/j.ejca.2005.03.018

    Article  CAS  PubMed  Google Scholar 

  14. Oda K, Matsuoka Y, Funahashi A, Kitano H (2005) A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol 1:2005.0010. doi:10.1038/msb4100014

    Article  PubMed Central  PubMed  Google Scholar 

  15. Abbitt KB, Rainger GE, Nash GB (2000) Effects of fluorescent dyes on selectin and integrin-mediated stages of adhesion and migration of flowing leukocytes. J Immunol Methods 239(1–2):109–119. doi:10.1016/S0022-1759(00)00189-7

    Article  CAS  PubMed  Google Scholar 

  16. Xi B, Yu N, Wang X, Xu X, Abassi Y (2008) The application of cell-based label-free technology in drug discovery. Biotechnol J 3(4):484–495. doi:10.1002/biot.200800020

    Article  CAS  PubMed  Google Scholar 

  17. Rodahl M, Kasemo B (1996) Frequency and dissipation-factor responses to localized liquid deposits on a QCM electrode. Sens Actuator B: Chem 37(1–2):111–116. doi:10.1016/S0925-4005(97)80077-9

    Article  CAS  Google Scholar 

  18. Sauerbrey G (1959) Verwendung von Schwingquarzen zur Wägung dünner Schichten und zur Mikrowägung. Zeitschrift für Physik 155(2):206–222. doi:10.1007/bf01337937

    Article  CAS  Google Scholar 

  19. Reviakine I, Johannsmann D, Richter RP (2011) Hearing what you cannot see and visualizing what you hear: interpreting quartz crystal microbalance data from solvated interfaces. Anal Chem 83(23):8838–8848. doi:10.1021/ac201778h

    Article  CAS  PubMed  Google Scholar 

  20. Zhang Y, Du B, Chen X, Ma H (2008) Convergence of dissipation and impedance analysis of quartz crystal microbalance studies. Anal Chem 81(2):642–648. doi:10.1021/ac8019762

    Article  Google Scholar 

  21. Cheng CI, Chang Y-P, Chu Y-H (2012) Biomolecular interactions and tools for their recognition: focus on the quartz crystal microbalance and its diverse surface chemistries and applications. Chem Soc Rev 41(5):1947–1971. doi:10.1039/c1cs15168a

    Article  CAS  PubMed  Google Scholar 

  22. Urbakh M, Tsionsky V, Gileadi E, Daikhin L (2007) Probing the solid/liquid interface with the quartz crystal microbalance. In: Janshoff A, Steinem C (eds) Piezoelectric sensors. Vol. 5. Springer series on chemical sensors and biosensors. Springer, Berlin, pp 111–149. doi:10.1007/978-3-540-36568-6_3

    Google Scholar 

  23. Höök F, Kasemo B (2007) The QCM-D technique for probing biomacromolecular recognition reactions. In: Janshoff A, Steinem C (eds) Piezoelectric sensors. Vol. 5. Springer series on chemical sensors and biosensors. Springer, Berlin, pp 425–447. doi:10.1007/978-3-540-36568-6_12

    Google Scholar 

  24. Marx K (2007) The quartz crystal microbalance and the electrochemical qcm: applications to studies of thin polymer films, electron transfer systems, biological macromolecules, biosensors, and cells. In: Steinem C, Janshoff A (eds) Piezoelectric sensors. Vol. 5. Springer series on chemical sensors and biosensors. Springer, Berlin, pp 371–424. doi:10.1007/5346_033

    Google Scholar 

  25. Hunter AC (2009) Application of the quartz crystal microbalance to nanomedicine. J Biomed Nanotechnol 5(6):669–675. doi:10.1166/jbn.2009.1083

    Article  CAS  PubMed  Google Scholar 

  26. Cabré EJ, Malmström J, Sutherland D, Pérez-Gil J, Otzen DE (2009) Surfactant protein sp-b strongly modifies surface collapse of phospholipid vesicles: insights from a quartz crystal microbalance with dissipation. Biophys J 97(3):768–776. doi:10.1016/j.bpj.2009.04.057

    Article  PubMed Central  PubMed  Google Scholar 

  27. Lee H-S, Contarino M, Umashankara M, Schön A, Freire E, Smith A III, Chaiken I, Penn L (2010) Use of the quartz crystal microbalance to monitor ligand-induced conformational rearrangements in HIV-1 envelope protein gp120. Anal Bioanal Chem 396(3):1143–1152. doi:10.1007/s00216-009-3313-8

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Keller CA, Kasemo B (1998) Surface specific kinetics of lipid vesicle adsorption measured with a quartz crystal microbalance. Biophys J 75(3):1397–1402. doi:10.1016/S0006-3495(98)74057-3

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Marques BF, Schneider JW (2005) Sequence-specific binding of DNA to liposomes containing di-alkyl peptide nucleic acid (PNA) amphiphiles. Langmuir 21(6):2488–2494. doi:10.1021/la047962u

    Article  CAS  PubMed  Google Scholar 

  30. Garcia M, Shahid A, Chen J, Xi J (2012) Evaluating inhibition of the epidermal growth factor (EGF)-induced response of mutant MCF-10A cells with an acoustic sensor. Biosensors 2(4):448–464. doi:10.3390/bios2040448

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Chen JY, Shahid A, Garcia MP, Penn LS, Xi J (2012) Dissipation monitoring for assessing EGF-induced changes of cell adhesion. Biosens Bioelectron 38(1):375–381

    Article  PubMed  Google Scholar 

  32. Chen JY, Li M, Penn LS, Xi J (2011) Real-time and label-free detection of cellular response to signaling mediated by distinct subclasses of epidermal growth factor receptors. Anal Chem 83(8):3141–3146. doi:10.1021/ac200160u

    Article  CAS  PubMed  Google Scholar 

  33. Xi J, Chen JY, Garcia MP, Penn LS (2013) Quartz crystal microbalance in cell biology studies. J Biochip Tissue Chip S5, 10.4172/2153-0777.S5-001

    Google Scholar 

  34. Höök F, Kasemo B, Nylander T, Fant C, Sott K, Elwing H (2001) Variations in coupled water, viscoelastic properties, and film thickness of a Mefp-1 protein film during adsorption and cross-linking: a quartz crystal microbalance with dissipation monitoring, ellipsometry, and surface plasmon resonance study. Anal Chem 73(24):5796–5804. doi:10.1021/ac0106501

    Article  PubMed  Google Scholar 

  35. Yin Y, Bilek MMM, McKenzie DR, Nosworthy NJ, Kondyurin A, Youssef H, Byrom MJ, Yang W (2009) Acetylene plasma polymerized surfaces for covalent immobilization of dense bioactive protein monolayers. Surf Coatings Technol 203(10–11):1310–1316. doi:10.1016/j.surfcoat.2008.10.035

    Article  CAS  Google Scholar 

  36. Hovgaard MB, Dong M, Otzen DE, Besenbacher F (2007) Quartz crystal microbalance studies of multilayer glucagon fibrillation at the solid-liquid interface. Biophys J 93(6):2162–2169. doi:10.1529/biophysj.107.109686

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Fredriksson C, Kihlman S, Rodahl M, Kasemo B (1998) The piezoelectric quartz crystal mass and dissipation sensor: a means of studying cell adhesion. Langmuir 14(2):248–251. doi:10.1021/la971005l

    Article  CAS  Google Scholar 

  38. Nimeri G, Fredriksson C, Elwing H, Liu L, Rodahl M, Kasemo B (1998) Neutrophil interaction with protein-coated surfaces studied by an extended quartz crystal microbalance technique. Colloids Surf B Biointerfaces 11(5):255–264.  doi:10.1016/S0927-7765(98)00038-1

    Article  CAS  Google Scholar 

  39. Saitakis M, Gizeli E (2012) Acoustic sensors as a biophysical tool for probing cell attachment and cell/surface interactions. Cell Mol Life Sci 69(3):357–371. doi:10.1007/s00018-011-0854-8

    Article  CAS  PubMed  Google Scholar 

  40. Yang R, Chen JY, Xi N, Lai KWC, Qu C, Fung CKM, Penn LS, Xi J (2012) Characterization of mechanical behavior of an epithelial monolayer in response to epidermal growth factor stimulation. Exp Cell Res 318(5):521–526. doi:10.1016/j.yexcr.2011.12.003

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Xi J, Penn LS, Chen JY, Xi N, Yang R (2012) Dynamic mechanical response of epithelial cells to epidermal growth factor. In: de Vicente J (ed) Viscoelasticity - From theory to biological applications. InTechOpen, pp 171–185. doi:10.5772/49977

  42. Xi N, Yang R, Song B, Lai KWC, Chen H, Chen JY, Penn LS, Xi J (2013) Developing a dynamics model for epidermal growth factor (EGF)-Induced cellular signaling events. In: Xi N, Zhang M, Li G (eds) Modeling and Control for Micro/Nano devices and systems. Automation and control engineering. CRC Press, pp 69–86. doi:10.1201/b16071-6

  43. Martin-Fernandez M, Clarke DT, Tobin MJ, Jones SV, Jones GR (2002) Preformed oligomeric epidermal growth factor receptors undergo an ectodomain structure change during signaling. Biophys J 82(5):2415–2427. doi:10.1016/S0006-3495(02)75585-9

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Fry DW, Nelson JM, Slintak V, Keller PR, Rewcastle GW, Denny WA, Zhou H, Bridges AJ (1997) Biochemical and antiproliferative properties of 4-[Ar(alk)ylamino]pyridopyrimidines, a new chemical class of potent and specific epidermal growth factor receptor tyrosine kinase inhibitor. Biochem Pharmacol 54(8):877–887. doi:10.1016/S0006-2952(97)00242-6

    Article  CAS  PubMed  Google Scholar 

  45. Gollob JA, Wilhelm S, Carter C, Kelley SL (2006) Role of Raf Kinase in Cancer: therapeutic potential of targeting the Raf/MEK/ERK signal transduction pathway. Semin Oncol 33(4):392–406.  doi:10.1053/j.seminoncol.2006.04.002

    Article  CAS  PubMed  Google Scholar 

  46. Vlahos CJ, Matter WF, Hui KY, Brown RF (1994) A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J Biol Chem 269(7):5241–5248

    CAS  PubMed  Google Scholar 

  47. Smith RJ, Sam LM, Justen JM, Bundy GL, Bala GA, Bleasdale JE (1990) Receptor-coupled signal transduction in human polymorphonuclear neutrophils: effects of a novel inhibitor of phospholipase C-dependent processes on cell responsiveness. J Pharmacol Exp Ther 253(2):688–697

    CAS  PubMed  Google Scholar 

  48. Garcia M, Shahid A, Chen J, Xi J (2013) Effects of the expression level of epidermal growth factor receptor on the ligand-induced restructuring of focal adhesions: a QCM-D study. Anal Bioanal Chem 405(4):1153–1158. doi:10.1007/s00216-012-6558-6

    Article  CAS  PubMed  Google Scholar 

  49. Le Guillou-Buffello D, Gindre M, Johnson P, Laugier P, Migonney V (2011) An alternative quantitative acoustical and electrical method for detection of cell adhesion process in real-time. Biotechnol Bioeng 108(4):947–962. doi:10.1002/bit.23005

    Article  PubMed  Google Scholar 

  50. Shelton JG, Moye PW, Steelman LS, Blalock WL, Lee JT, Franklin RA, McMahon M, McCubrey JA (2003) Differential effects of kinase cascade inhibitors on neoplastic and cytokine-mediated cell proliferation. Leukemia 17(9):1765–1782. doi:10.1038/sj.leu.2403052

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, Drexel University, 3141 Chestnut Street, Philadelphia, PA, 19104, USA

    Jennifer Y. Chen, Marcela P. Garcia, Lynn S. Penn & Jun Xi

Authors
  1. Jennifer Y. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marcela P. Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lynn S. Penn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jun Xi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jun Xi .

Editor information

Editors and Affiliations

  1. Biochemical Technologies, Science and Technology Division, Corning Incorporated, Corning, New York, USA

    Ye Fang

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this protocol

Cite this protocol

Chen, J.Y., Garcia, M.P., Penn, L.S., Xi, J. (2015). Use of the Quartz Crystal Microbalance with Dissipation Monitoring for Pharmacological Evaluation of Cell Signaling Pathways Mediated by Epidermal Growth Factor Receptors. In: Fang, Y. (eds) Label-Free Biosensor Methods in Drug Discovery. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2617-6_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2617-6_14

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2616-9

  • Online ISBN: 978-1-4939-2617-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation