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. 1998 Aug;75(2):583–594. doi: 10.1016/S0006-3495(98)77549-6

Extending the range of rate constants available from BIACORE: interpreting mass transport-influenced binding data.

D G Myszka 1, X He 1, M Dembo 1, T A Morton 1, B Goldstein 1
PMCID: PMC1299734  PMID: 9675161

Abstract

Surface-based binding assays are often influenced by the transport of analyte to the sensor surface. Using simulated data sets, we test a simple two-compartment model to see if its description of transport and binding is sufficient to accurately analyze BIACORE data. First we present a computer model that can generate realistic BIACORE data. This model calculates the laminar flow of analyte within the flow cell, its diffusion both perpendicular and parallel to the sensor surface, and the reversible chemical reaction between analyte and immobilized reactant. We use this computer model to generate binding data under a variety of conditions. An analysis of these data sets with the two-compartment model demonstrates that good estimates of the intrinsic reaction rate constants are recovered even when mass transport influences the binding reaction. We also discuss the conditions under which the two-compartment model can be used to determine the diffusion coefficient of the analyte. Our results illustrate that this model can significantly extend the range of association rate constants that can be accurately determined from BIACORE.

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Selected References

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  1. Brody J. P., Yager P., Goldstein R. E., Austin R. H. Biotechnology at low Reynolds numbers. Biophys J. 1996 Dec;71(6):3430–3441. doi: 10.1016/S0006-3495(96)79538-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chaiken I., Rosé S., Karlsson R. Analysis of macromolecular interactions using immobilized ligands. Anal Biochem. 1992 Mar;201(2):197–210. doi: 10.1016/0003-2697(92)90329-6. [DOI] [PubMed] [Google Scholar]
  3. Christensen L. L. Theoretical analysis of protein concentration determination using biosensor technology under conditions of partial mass transport limitation. Anal Biochem. 1997 Jul 1;249(2):153–164. doi: 10.1006/abio.1997.2182. [DOI] [PubMed] [Google Scholar]
  4. Fivash M., Towler E. M., Fisher R. J. BIAcore for macromolecular interaction. Curr Opin Biotechnol. 1998 Feb;9(1):97–101. doi: 10.1016/s0958-1669(98)80091-8. [DOI] [PubMed] [Google Scholar]
  5. Garland P. B. Optical evanescent wave methods for the study of biomolecular interactions. Q Rev Biophys. 1996 Feb;29(1):91–117. doi: 10.1017/s0033583500005758. [DOI] [PubMed] [Google Scholar]
  6. Glaser R. W. Antigen-antibody binding and mass transport by convection and diffusion to a surface: a two-dimensional computer model of binding and dissociation kinetics. Anal Biochem. 1993 Aug 15;213(1):152–161. doi: 10.1006/abio.1993.1399. [DOI] [PubMed] [Google Scholar]
  7. Ito W., Kurosawa Y. Development of an artificial antibody system with multiple valency using an Fv fragment fused to a fragment of protein A. J Biol Chem. 1993 Sep 25;268(27):20668–20675. [PubMed] [Google Scholar]
  8. Karlsson R., Fält A. Experimental design for kinetic analysis of protein-protein interactions with surface plasmon resonance biosensors. J Immunol Methods. 1997 Jan 15;200(1-2):121–133. doi: 10.1016/s0022-1759(96)00195-0. [DOI] [PubMed] [Google Scholar]
  9. Malmborg A. C., Michaëlsson A., Ohlin M., Jansson B., Borrebaeck C. A. Real time analysis of antibody-antigen reaction kinetics. Scand J Immunol. 1992 Jun;35(6):643–650. doi: 10.1111/j.1365-3083.1992.tb02970.x. [DOI] [PubMed] [Google Scholar]
  10. Malmqvist M. Surface plasmon resonance for detection and measurement of antibody-antigen affinity and kinetics. Curr Opin Immunol. 1993 Apr;5(2):282–286. doi: 10.1016/0952-7915(93)90019-o. [DOI] [PubMed] [Google Scholar]
  11. Morton T. A., Bennett D. B., Appelbaum E. R., Cusimano D. M., Johanson K. O., Matico R. E., Young P. R., Doyle M., Chaiken I. M. Analysis of the interaction between human interleukin-5 and the soluble domain of its receptor using a surface plasmon resonance biosensor. J Mol Recognit. 1994 Mar;7(1):47–55. doi: 10.1002/jmr.300070107. [DOI] [PubMed] [Google Scholar]
  12. Morton T. A., Myszka D. G., Chaiken I. M. Interpreting complex binding kinetics from optical biosensors: a comparison of analysis by linearization, the integrated rate equation, and numerical integration. Anal Biochem. 1995 May 1;227(1):176–185. doi: 10.1006/abio.1995.1268. [DOI] [PubMed] [Google Scholar]
  13. Myszka D. G., Arulanantham P. R., Sana T., Wu Z., Morton T. A., Ciardelli T. L. Kinetic analysis of ligand binding to interleukin-2 receptor complexes created on an optical biosensor surface. Protein Sci. 1996 Dec;5(12):2468–2478. doi: 10.1002/pro.5560051209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Myszka D. G., Morton T. A., Doyle M. L., Chaiken I. M. Kinetic analysis of a protein antigen-antibody interaction limited by mass transport on an optical biosensor. Biophys Chem. 1997 Feb 28;64(1-3):127–137. doi: 10.1016/s0301-4622(96)02230-2. [DOI] [PubMed] [Google Scholar]
  15. Myszka DG. Kinetic analysis of macromolecular interactions using surface plasmon resonance biosensors. Curr Opin Biotechnol. 1997 Feb 1;8(1):50–57. doi: 10.1016/s0958-1669(97)80157-7. [DOI] [PubMed] [Google Scholar]
  16. Parsons I. D., Stockley P. G. Quantitation of the Escherichia coli methionine repressor-operator interaction by surface plasmon resonance is not affected by the presence of a dextran matrix. Anal Biochem. 1997 Dec 1;254(1):82–87. doi: 10.1006/abio.1997.2356. [DOI] [PubMed] [Google Scholar]
  17. Raghavan M., Bjorkman P. J. BIAcore: a microchip-based system for analyzing the formation of macromolecular complexes. Structure. 1995 Apr 15;3(4):331–333. doi: 10.1016/s0969-2126(01)00164-2. [DOI] [PubMed] [Google Scholar]
  18. Roden L. D., Myszka D. G. Global analysis of a macromolecular interaction measured on BIAcore. Biochem Biophys Res Commun. 1996 Aug 23;225(3):1073–1077. doi: 10.1006/bbrc.1996.1297. [DOI] [PubMed] [Google Scholar]
  19. Schuck P. Kinetics of ligand binding to receptor immobilized in a polymer matrix, as detected with an evanescent wave biosensor. I. A computer simulation of the influence of mass transport. Biophys J. 1996 Mar;70(3):1230–1249. doi: 10.1016/S0006-3495(96)79681-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schuck P., Minton A. P. Analysis of mass transport-limited binding kinetics in evanescent wave biosensors. Anal Biochem. 1996 Sep 5;240(2):262–272. doi: 10.1006/abio.1996.0356. [DOI] [PubMed] [Google Scholar]
  21. Schuck P. Reliable determination of binding affinity and kinetics using surface plasmon resonance biosensors. Curr Opin Biotechnol. 1997 Aug;8(4):498–502. doi: 10.1016/s0958-1669(97)80074-2. [DOI] [PubMed] [Google Scholar]
  22. Schuck P. Use of surface plasmon resonance to probe the equilibrium and dynamic aspects of interactions between biological macromolecules. Annu Rev Biophys Biomol Struct. 1997;26:541–566. doi: 10.1146/annurev.biophys.26.1.541. [DOI] [PubMed] [Google Scholar]
  23. Sjölander S., Urbaniczky C. Integrated fluid handling system for biomolecular interaction analysis. Anal Chem. 1991 Oct 15;63(20):2338–2345. doi: 10.1021/ac00020a025. [DOI] [PubMed] [Google Scholar]
  24. Straume M., Johnson M. L. Monte Carlo method for determining complete confidence probability distributions of estimated model parameters. Methods Enzymol. 1992;210:117–129. doi: 10.1016/0076-6879(92)10009-3. [DOI] [PubMed] [Google Scholar]
  25. Szabo A., Stolz L., Granzow R. Surface plasmon resonance and its use in biomolecular interaction analysis (BIA). Curr Opin Struct Biol. 1995 Oct;5(5):699–705. doi: 10.1016/0959-440x(95)80064-6. [DOI] [PubMed] [Google Scholar]
  26. Wohlhueter R. M., Parekh K., Udhayakumar V., Fang S., Lal A. A. Analysis of binding of monoclonal antibody to a malarial peptide by surface plasmon resonance biosensor and integrated rate equations. J Immunol. 1994 Jul 1;153(1):181–189. [PubMed] [Google Scholar]
  27. Yarmush M. L., Patankar D. B., Yarmush D. M. An analysis of transport resistances in the operation of BIAcore; implications for kinetic studies of biospecific interactions. Mol Immunol. 1996 Oct;33(15):1203–1214. doi: 10.1016/s0161-5890(96)00075-2. [DOI] [PubMed] [Google Scholar]
  28. van der Merwe P. A., Barclay A. N. Analysis of cell-adhesion molecule interactions using surface plasmon resonance. Curr Opin Immunol. 1996 Apr;8(2):257–261. doi: 10.1016/s0952-7915(96)80065-3. [DOI] [PubMed] [Google Scholar]

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