Display options
Cite
de Oliveira LR, Jaqaman K. FISIK: Framework for the Inference of In Situ Interaction Kinetics from Single-Molecule Imaging Data. Biophys J. 2019;117(6):1012-1028doi: 10.1016/j.bpj.2019.07.050.
de Oliveira, L. R., & Jaqaman, K. (2019). FISIK: Framework for the Inference of In Situ Interaction Kinetics from Single-Molecule Imaging Data. Biophysical journal, 117(6), 1012-1028. https://doi.org/10.1016/j.bpj.2019.07.050
de Oliveira, Luciana R, and Jaqaman, Khuloud. "FISIK: Framework for the Inference of In Situ Interaction Kinetics from Single-Molecule Imaging Data." Biophysical journal vol. 117,6 (2019): 1012-1028. doi: https://doi.org/10.1016/j.bpj.2019.07.050
de Oliveira LR, Jaqaman K. FISIK: Framework for the Inference of In Situ Interaction Kinetics from Single-Molecule Imaging Data. Biophys J. 2019 Sep 17;117(6):1012-1028. doi: 10.1016/j.bpj.2019.07.050. Epub 2019 Aug 06. PMID: 31443908; PMCID: PMC6818184.
Copy Download .nbib Format: NLM
Share it on

Biophys J. 2019 Sep 17;117(6):1012-1028. doi: 10.1016/j.bpj.2019.07.050. Epub 2019 Aug 06.

FISIK: Framework for the Inference of In Situ Interaction Kinetics from Single-Molecule Imaging Data.

Biophysical journal

Luciana R de Oliveira, Khuloud Jaqaman

Affiliations

  1. Department of Biophysics, UT Southwestern Medical Center, Dallas, Texas.
  2. Department of Biophysics, UT Southwestern Medical Center, Dallas, Texas; Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, Texas. Electronic address: [email protected].

PMID: 31443908 PMCID: PMC6818184 DOI: 10.1016/j.bpj.2019.07.050

Abstract

Recent experimental and computational developments have been pushing the limits of live-cell single-molecule imaging, enabling the monitoring of intermolecular interactions in their native environment with high spatiotemporal resolution. However, interactions are captured only for the labeled subset of molecules, which tends to be a small fraction. As a result, it has remained a challenge to calculate molecular interaction kinetics, in particular association rates, from live-cell single-molecule tracking data. To overcome this challenge, we developed a mathematical modeling-based Framework for the Inference of in Situ Interaction Kinetics (FISIK) from single-molecule imaging data with substoichiometric labeling. FISIK consists of (I) devising a mathematical model of molecular movement and interactions, mimicking the biological system and data-acquisition setup, and (II) estimating the unknown model parameters, including molecular association and dissociation rates, by fitting the model to experimental single-molecule data. Due to the stochastic nature of the model and data, we adapted the method of indirect inference for model calibration. We validated FISIK using a series of tests in which we simulated trajectories of diffusing molecules that interact with each other, considering a wide range of model parameters, and including resolution limitations, tracking errors, and mismatches between the model and the biological system it mimics. We found that FISIK has the sensitivity to determine association and dissociation rates, with accuracy and precision depending on the labeled fraction of molecules and the extent of molecule tracking errors. For cases where the labeled fraction is too low (e.g., to afford accurate tracking), combining dynamic but sparse single-molecule imaging data with almost-whole population oligomer distribution data improves FISIK's performance. All in all, FISIK is a promising approach for the derivation of molecular interaction kinetics in their native environment from single-molecule imaging data with substoichiometric labeling.

Copyright © 2019 Biophysical Society. Published by Elsevier Inc. All rights reserved.

References

  1. Nat Chem Biol. 2012 Sep;8(9):774-83 - PubMed
  2. Nat Struct Mol Biol. 2011 Oct 23;18(11):1244-9 - PubMed
  3. Chem Rev. 2009 Mar 11;109(3):839-60 - PubMed
  4. J R Soc Interface. 2009 Feb 6;6(31):187-202 - PubMed
  5. Nat Commun. 2019 Jan 17;10(1):272 - PubMed
  6. Nat Rev Mol Cell Biol. 2006 Nov;7(11):813-9 - PubMed
  7. J Cell Biol. 2011 Feb 7;192(3):463-80 - PubMed
  8. Phys Biol. 2004 Dec;1(3-4):137-51 - PubMed
  9. IEEE Trans Pattern Anal Mach Intell. 2015 Mar;37(3):611-24 - PubMed
  10. Nature. 2010 Feb 18;463(7283):963-7 - PubMed
  11. Cell Syst. 2017 Feb 22;4(2):194-206.e9 - PubMed
  12. Ecol Lett. 2011 Aug;14(8):816-27 - PubMed
  13. Nat Methods. 2014 Mar;11(3):281-9 - PubMed
  14. Biophys J. 2012 Jun 6;102(11):L41-3 - PubMed
  15. Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):743-8 - PubMed
  16. J Cell Biol. 2002 Jun 10;157(6):1071-81 - PubMed
  17. Nat Methods. 2013 May;10(5):421-6 - PubMed
  18. Exp Cell Res. 2011 Apr 15;317(7):955-65 - PubMed
  19. Biophys J. 2015 Aug 18;109(4):710-21 - PubMed
  20. J Chem Phys. 2018 Mar 28;148(12):123328 - PubMed
  21. Biophys J. 2012 Jul 18;103(2):L17-9 - PubMed
  22. Biophys J. 2008 Dec 15;95(12):5988-6001 - PubMed
  23. Cell. 2011 Aug 19;146(4):593-606 - PubMed
  24. PLoS Comput Biol. 2007 Jun;3(6):e101 - PubMed
  25. Ann Hematol. 2014 Feb;93(2):181-92 - PubMed
  26. J Comput Biol. 2012 Jun;19(6):606-18 - PubMed
  27. Biochim Biophys Acta. 2014 Jun;1840(6):2014-24 - PubMed
  28. Nature. 2017 Oct 26;550(7677):543-547 - PubMed
  29. Curr Protoc Cytom. 2016 Jan 06;75:1.29.1-1.29.14 - PubMed
  30. Nat Methods. 2018 Jan;15(1):47-51 - PubMed
  31. J Immunol Methods. 2015 Mar;418:66-74 - PubMed
  32. Interface Focus. 2011 Dec 6;1(6):807-20 - PubMed
  33. Nature. 2010 Apr 8;464(7290):932-6 - PubMed
  34. Nat Methods. 2011 Apr;8(4):279-80 - PubMed
  35. ACS Sens. 2018 Sep 28;3(9):1735-1742 - PubMed
  36. Science. 2003 Jun 27;300(5628):2061-5 - PubMed
  37. Biophys J. 2007 Apr 15;92(8):2926-43 - PubMed
  38. Bull Math Biol. 2008 Aug;70(6):1707-29 - PubMed
  39. PLoS One. 2013 May 22;8(5):e64320 - PubMed
  40. Sci Rep. 2014 Apr 03;4:4577 - PubMed
  41. Sci Rep. 2015 Sep 11;5:14072 - PubMed
  42. Trends Pharmacol Sci. 2018 Feb;39(2):109-122 - PubMed
  43. Nat Methods. 2008 Aug;5(8):695-702 - PubMed
  44. Eur J Immunol. 2015 Jul;45(7):2099-110 - PubMed
  45. Sci Signal. 2017 Oct 31;10(503):null - PubMed

MeSH terms

Publication Types

Grant support