Anomalous Subdiffusive Measurements by Fluorescence Correlations Spectroscopy and Simulations of Translational Diffusive Behavior in Live Cells
Main Article Content
Keywords
Live cells, anomalous translational diffusion, subdiffusive transport, simulation, fluorescence correlation spectroscopy, fluorescence fluctuation spectroscopy, FCS, autocorrelation function of fluorescence intensity fluctuations
Abstract
Using a combination of optical experiments and computer simulations, we found that live cells act as traps to produce anomalous subdiffusive translational motion of molecules exemplified by the glucocorticoid receptor α. The glucocorticoid receptor α was expressed as a fusion protein with the green fluorescent protein in living mammalian U2OS cells. The measurements were carried out by fluorescence correlation spectroscopy. The glucocorticoid receptor α was either a homodimer or a monomer in the nucleoplasm depending on the presence or absence of the stimulus dexamethasone. Our simulations showed that the experimentally measured rates of translational diffusion could be attributed to spatial and temporal traps. Thus, traps acted by spatial and temporal heterogeneity and randomness, respectively. As we prove here for the first time, anomalous translational diffusion caused by spatial randomness was different from anomalous translational diffusion caused by heterogeneous temporal randomness. For this purpose, we explored two classes of transformations in the time domain for which the assumption that they are stable and have probability density functions was satisfied. The first one was the Inverse Gamma distribution and the second class was a stable Levy distribution. The spatial exponent α that was extracted from time series expressed scale invariance in the space domain. The time exponent γ measured limited time scaling of the embedding complex dynamics. Hence, both exponents must not be mixed up by a single exponent. Fluorescence fluctuation spectroscopy (FCS) is the method of choice for measuring the exponents of anomalous subdiffusive translational motion of molecules in live cells.
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References
1. Baumann G, Place RF, Földes-Papp Z (2010) Meaningful interpretation of subdiffusive measurements in living cells (crowded environment) by fluorescence fluctuation microscopy. Curr Pharm Biotechnol 11 (5): 527-543.
2. Földes-Papp Z, Baumann G (2011) Fluorescence molecule counting for single-molecule studies in crowded environment of living cells without and with broken ergodicity. Curr Pharm Biotechnol 12 (5): 824-833.
3. Földes-Papp Z, Angerer B, Ankenbauer W, Baumann G, Birch-Hirschfeld E, et al. (1996) Modeling the dynamics of nonenzymatic and enzymatic nucleotide processes by fractal dimension. In: Losa GA, Merlini D, Nonnenmacher TF, Weibel ER, editors. Fractals in Biology and Medicine, vol 2. Boston: Birkhauser. pp. 238-254.
4. Földes-Papp Z, Thyberg P, Björling S, Holmgen A, Rigler R (1997) Exonuclease degradation of DNA studied by fluorescence correlation spectroscopy. Nucleosides, Nucleotides & Nucleic Acids 16 (5-6): 781-787.
5. Axelrod D, Koppel DE, Schlessinger J, Elson E, Webb WW (1976) Mobility measurement by analysis of fluorescence photobleaching recovery kinetics. Biophys J 16: 1055–1069.
6. Rich RM, Mummert M, Gryczynski Z, Borejdo J, Sørensen TJ, et al. (2013) Elimination of autofluorescence in fluorescence correlation spectroscopy by using the AzaDiOxaTriAngulenium (ADOTA) fluorophore in combination with time correlated single photon counting (TCSPC). Anal Bioanal Chem 405 (14): 4887-4894.
7. Rich RM, Mummert M, Földes-Papp Z, Gryczynski Z, Borejdo J, et al. (2012) Detection of hyaluronidase activity using fluorescein labeled hyaluronic acid and fluorescence correlation spectroscopy. J Photochem Photobiol B 116: 7-12.
8. Földes-Papp Z, Liao S-CJ, You T, Terpetschnig E, Barbieri B (2010) Confocal fluctuation spectroscopy and imaging. Curr Pharm Biotechnol 11 (6): 639-653.
9. Földes-Papp Z (2009) Viral chip technology in genomic medicine. In: Willard WF, Ginsburg GS, editors. Handbook of genomic and personalized medicine, vol 2. New York: Elsevier. pp. 538-561.
10. Földes-Papp Z, Kinjo M, Tamura M, Birch-Hirschfeld E, Demel U, et al. (2005) A new ultrasensitive way to circumvent PCR-based allele distinction: direct probing of unamplified genomic DNA by solution-phase hybridization using two-color fluorescence cross-correlation spectroscopy. Exp Mol Pathol 78 (3): 177-189.
11. Földes-Papp Z, Costa JM, Demel U, Tilz GP., Kinjo M, et al. (2004) Specifically associated PCR products probed by coincident detection of two-color cross-correlated fluorescence intensities in human gene polymorphisms of methylene tetrahydrofolate reductase at site C677T: a novel measurement approach without follow-up mathematical analysis. Exp Mol Pathol 76 (3): 212-218.
12. Földes-Papp Z, Demel U, Tilz GP (2004) A new concept for ultrasensitive fluorescence measurements of molecules in solution and membrane: 1. Theory and a first application. J Immunol Methods 286 (1-2): 1-11.
13. Földes-Papp Z, Demel U, Tilz GP (2004) A new concept for ultrasensitive fluorescence measurements of molecules in solution and membrane: 2. The individual immune molecule. J Immunol Methods 286 (1-2): 13-20.
14. Földes-Papp Z, Kinjo M, Saito K, Kii H, Takagi T, et al. (2003) C677T single nucleotide polymorphisms of the human methylene tetrahydrofolate reductase and specific identification : a novel strategy using two-color cross-correlation fluorescence spectroscopy. Mol Diagn 7 (2): 99-111.
15. Földes-Papp Z, Demel U, Domej W, Tilz GP (2002) A new dimension for the development of fluorescence-based assays in solution: From Physical Principles of FCS Detection to Biological Applications. Exp Biol Med 227 (5): 291-300.
16. Földes-Papp Z, Demel U, Tilz GP (2002). Detection of single molecules: solution-phase single-molecule fluorescence correlation spectroscopy as an ultrasensitive, rapid and reliable system for immunological investigation. J Immunol Methods 260 (1-2): 117-124.
17. Jermutus L, Kolly R, Földes-Papp Z, Hanes J, Rigler R, et al. (2002) Ligand binding of a ribosome-displayed protein detected in solution at the single molecule level by fluorescence correlation spectroscopy. Eur Biophys J 31 (3): 179-184.
18. Földes-Papp Z, Demel U, Tilz GP (2001) Ultrasensitive detection and identification of fluorescent molecules by FCS: impact for immunobiology. Proc Natl Acad Sci USA 98 (20): 11509-11514.
19. Stephan J, Dörre K, Brakmann S,Winkler T, Wetzel T, et al. (2001) Towards a general procedure for sequencing single DNA molecules. J Biotechnol 86 (3): 255-267.
20. Földes-Papp Z, Angerer B, Ankenbauer W, Rigler R (2001) Fluorescent high-density labeling of DNA: error-free substitution for a normal nucleotide. J Biotechnol 86 (3): 237-253.
21. Földes-Papp Z, Angerer B, Thyberg P, Hinz M, Wennmalm S, et al. (2001) Fluorescently labeled model DNA sequences for exonucleolytic sequencing. J Biotechnol 86 (3): 203-224.
22. Földes-Papp Z, Kinjo M (2001) Fluorescence correlation spectroscopy in nucleic acids analysis. In: Elson E, Rigler R, editors. Fluorescence correlation spectroscopy: theory and applications. Springer series in physical chemistry, vol 65. Boston: Springer. pp. 25-64.
23. Lagerkvist AC, Földes-Papp Z, Persson MA, Rigler R (2001) Fluorescence correlation spectroscopy as a method for assessment of interactions between phage displaying antibodies and soluble antigen. Protein Sci 10 (8): 1522-1528.
24. Földes-Papp Z, Rigler R (2001) Quantitative two-color fluorescence cross-correlation spectroscopy in the analysis of polymerase chain reaction. Biol Chem 382 (3): 473-478.
25. Bark N, Földes-Papp Z, Rigler R (1999) The incipient stage in thrombin-induced fibrin polymerization detected by FCS at the single molecule level. Biochem Biophys Res Commun 260 (1): 35-41.
26. Rigler R, Földes-Papp Z, Meyer-Almes FJ, Sammet C, Völcker M, et al. (1998) Fluorescence cross-correlation: a new concept for polymerase chain reaction. J Biotechnol 63 (2): 97-109.
27. Baumann G, Gryczynski I. Földes-Papp Z (2010) Anomalous behavior in length distributions of 3D random Brownian walks and measured photon count rates within observation volumes of single-molecule trajectories in fluorescence fluctuation microscopy. Optics Express 18 (17): 17883-17896.
28. Zustiak SP, Nossal R, Sackett DL (2011) Hindered diffusion in polymeric solutions studied by fluorescence correlation spectroscopy. Biophys J 101 (1): 255–264.
29. Braet C, Stephan H, Dobbie IM, Togashi DM, Ryder AG, et al. (2007) Mobility and distribution of replication protein A in living cells using fluorescence correlation spectroscopy. Exp Mol Pathol 82 (2): 156-162.
30. Feder TJ, Brust-Mascher I, Slattery JP, Baird B, Webb WW (1996) Constrained diffusion or immobile fraction of cell surfaces: a new interpretation. Biophys J 70: 2767-2773.
31. Schwille P, Haupts U, Maiti S, Webb WW (1999) Molecular dynamics in living cells observed by fluorescence correlation spectroscopy with one- and two-photon excitation. Biophys J 77: 2251-2265.
32. Wu J, Berland KM (2008) Propagators and time-dependent diffusion coefficients for anomalous diffusion. Biophys J 95: 2049-2052.
33. Dix JA, Verkman AS (2008) Crowding effects on diffusion in solution and cells. Annu Rev Biophys 37: 247-263.
34. Szymanski J, Weiss, W (2009) Elucidating the origin of anomalous diffusion in crowded fluids. Phys Rev Lett 103: 038102.
35. Földes-Papp Z (2006) What it means to measure a single molecule in a solution by fluorescence fluctuation spectroscopy. Ex Mol Pathol 80 (3): 209-218.
36. Földes-Papp Z (2007) ‘True’ single-molecule molecule observations by fluorescence correlation spectroscopy and two-color fluorescence cross-correlation spectroscopy. Exp Mol Pathol 82 (2): 147-155.
37. Meroz Y, Sokolov IM, Klafter J (2010) Subdiffusion of mixed origins: when ergodicity and nonergodicity coexist. Phys Rev E 81: 010101(R).
38. Sokolov IM (2012) Models of anomalous diffusion in crowded environments. Soft Matter 8: 9043–9052.
39. Weigel AV, Simon B, Tamkun MM, Krapf D (2011) Ergodic and nonergodic processes coexist in the plasma membrane as observed by single-molecule tracking. Proc Natl Acad Sci US.A 108 (16): 6438–6443.
40. Heitzer MD, Wolf IM, Sanchez ER, Witchel SF, DeFranco DB (2007) Glucocorticoid receptor physiology. Rev Endocr Metab Disord 8: 321-330.
41. Mikuni S, Tamura M, Kinjo M (2007) Analysis of intranuclear binding process of glucocorticoid receptor using fluorescence correlation spectroscopy. FEBS Lett 581: 389-393.
42. Cheung J, Smith F (2000) Molecular chaperone interactions with steroid receptors: an update. Mol Endocrinol 14: 939-946.
43. McNally JG, Muller WG, Walker D, Wolford R, Hager GL (2000) The glucocorticoid receptor: rapid exchange with regulatory sites in living cells. Science 287: 1262-1265.
44. De Bosscher K, Haegeman G (2009) Minireview: Latest perspectives on antiinflammatory actions of glucocorticoids. Mol Endocrinol 23: 281-291.
45. Vandevyver S, Dejager L, Libert C (2012) On the trail of the glucocorticoid receptor: into the nucleus and back. Traffic 13: 364-374.
46. Silverman MN, Mukhopadhyay P, Belyavskaya E, Tonelli LH, Revenis BD, et al. (2013) Glucocorticoid receptor dimerization is required for proper recovery of LPS-induced inflammation, sickness behavior and metabolism in mice. Mol Psychiatry 18 (9): 1006-1017.
47. Magde D, Elson E., Webb WW (1972) Thermodynamic fluctuations in a reacting system: measurement by fluorescence correlation spectroscopy. Phys Rev Lett 29: 705–708
48. Eigen M, Rigler R (1994) Sorting single molecules: application to diagnostics and evolutionary biotechnology. Proc Natl Acad Sci USA 91 (57): 40–47.
49. Barkai E, Metzler R, Klafter J (2000) From continuous time random walks to the fractional Fokker-Planck equation. Phys Rev E, 61: 132–138.
50. Metzler R, Klafter J (2000) The random walker's guide to anomalous diffusion: a fractal dynamics approach. Phys Rep 339: 1–77.
51. Havlin S, Ben-Avraham D (1987) Diffusion in disordered media. Adv Phys 36: 695–798.
52. Gebhardt JC, Suter DM, Roy R, Zhao ZW, Chapman AR, et al. (2013) Single-molecule imaging of transcription factor binding to DNA in live mammalian cells. Nat Methods 10 (5): 421-426.
53. Mazza D, Mueller F, Stasevich TJ, McNally JG (2013) Convergence of chromatin binding estimates in live cells. Nat Methods 10 (8): 691-692.
54. Kleiman A, Hübner S, Rodriguez Parkitna JM, Neumann A, Hofer S, et al. (2012) Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages. FASEB J 26 (2): 722-729.
55. Földes-Papp Z (2013) Measurements of single molecules in solution and live cells over longer observation times than those currently possible: the meaningful time. Curr Pharm Biotechnol 14 (4): 441-444.
56. Földes-Papp Z (2005) How the molecule number is correctly quantified in two-color fluorescence cross-correlation spectroscopy: corrections for cross-talk and quenching in experiments. Curr Pharm Biotechnol 6 ( 6): 437-444.
57. Földes-Papp Z (2007) Fluorescence fluctuation spectroscopic approaches to the study of a single molecule diffusing in solution and a live cell without systemic drift or convection: a theoretical study. Curr Pharm Biotechnol 8(5): 261-273.
58. Digman MA., Gratton E (2011) Lessons in fluctuation correlation spectroscopy. Annu Rev Phys Chem 62: 645-668.
59. Di Rienzo C, Gratton E, Beltram F, Cardarelli F (2013) Fast spatiotemporal correlation spectroscopy to determine protein lateral diffusion laws in live cell membranes. Proc Natl Acad Sci USA 110 (30): 12307-12312.
60. Digman MA, Gratton E (2009) Imaging barriers to diffusion by pair correlation functions. Biophys J 97: 665–673.
61. Cardarelli F, Gratton E (2010) In vivo imaging of single-molecule translocation through nuclear pore complexes by pair correlation functions. PLoS One 5 (5): e10475.
62 Földes-Papp Z (2002) Theory of measuring the selfsame single fluorescent molecule in solution suited for studying individual molecular interactions by SPSM-FCS Pteridines 13: 73-82.
63. Földes-Papp Z, Baumann G, Demel U, Tilz GP (2004) Counting and behavior of an individual fluorescent molecule without hydrodynamic flow, immobilization, or photon count statistics. Curr Pharm Biotechnol 5 (2): 163-172.
2. Földes-Papp Z, Baumann G (2011) Fluorescence molecule counting for single-molecule studies in crowded environment of living cells without and with broken ergodicity. Curr Pharm Biotechnol 12 (5): 824-833.
3. Földes-Papp Z, Angerer B, Ankenbauer W, Baumann G, Birch-Hirschfeld E, et al. (1996) Modeling the dynamics of nonenzymatic and enzymatic nucleotide processes by fractal dimension. In: Losa GA, Merlini D, Nonnenmacher TF, Weibel ER, editors. Fractals in Biology and Medicine, vol 2. Boston: Birkhauser. pp. 238-254.
4. Földes-Papp Z, Thyberg P, Björling S, Holmgen A, Rigler R (1997) Exonuclease degradation of DNA studied by fluorescence correlation spectroscopy. Nucleosides, Nucleotides & Nucleic Acids 16 (5-6): 781-787.
5. Axelrod D, Koppel DE, Schlessinger J, Elson E, Webb WW (1976) Mobility measurement by analysis of fluorescence photobleaching recovery kinetics. Biophys J 16: 1055–1069.
6. Rich RM, Mummert M, Gryczynski Z, Borejdo J, Sørensen TJ, et al. (2013) Elimination of autofluorescence in fluorescence correlation spectroscopy by using the AzaDiOxaTriAngulenium (ADOTA) fluorophore in combination with time correlated single photon counting (TCSPC). Anal Bioanal Chem 405 (14): 4887-4894.
7. Rich RM, Mummert M, Földes-Papp Z, Gryczynski Z, Borejdo J, et al. (2012) Detection of hyaluronidase activity using fluorescein labeled hyaluronic acid and fluorescence correlation spectroscopy. J Photochem Photobiol B 116: 7-12.
8. Földes-Papp Z, Liao S-CJ, You T, Terpetschnig E, Barbieri B (2010) Confocal fluctuation spectroscopy and imaging. Curr Pharm Biotechnol 11 (6): 639-653.
9. Földes-Papp Z (2009) Viral chip technology in genomic medicine. In: Willard WF, Ginsburg GS, editors. Handbook of genomic and personalized medicine, vol 2. New York: Elsevier. pp. 538-561.
10. Földes-Papp Z, Kinjo M, Tamura M, Birch-Hirschfeld E, Demel U, et al. (2005) A new ultrasensitive way to circumvent PCR-based allele distinction: direct probing of unamplified genomic DNA by solution-phase hybridization using two-color fluorescence cross-correlation spectroscopy. Exp Mol Pathol 78 (3): 177-189.
11. Földes-Papp Z, Costa JM, Demel U, Tilz GP., Kinjo M, et al. (2004) Specifically associated PCR products probed by coincident detection of two-color cross-correlated fluorescence intensities in human gene polymorphisms of methylene tetrahydrofolate reductase at site C677T: a novel measurement approach without follow-up mathematical analysis. Exp Mol Pathol 76 (3): 212-218.
12. Földes-Papp Z, Demel U, Tilz GP (2004) A new concept for ultrasensitive fluorescence measurements of molecules in solution and membrane: 1. Theory and a first application. J Immunol Methods 286 (1-2): 1-11.
13. Földes-Papp Z, Demel U, Tilz GP (2004) A new concept for ultrasensitive fluorescence measurements of molecules in solution and membrane: 2. The individual immune molecule. J Immunol Methods 286 (1-2): 13-20.
14. Földes-Papp Z, Kinjo M, Saito K, Kii H, Takagi T, et al. (2003) C677T single nucleotide polymorphisms of the human methylene tetrahydrofolate reductase and specific identification : a novel strategy using two-color cross-correlation fluorescence spectroscopy. Mol Diagn 7 (2): 99-111.
15. Földes-Papp Z, Demel U, Domej W, Tilz GP (2002) A new dimension for the development of fluorescence-based assays in solution: From Physical Principles of FCS Detection to Biological Applications. Exp Biol Med 227 (5): 291-300.
16. Földes-Papp Z, Demel U, Tilz GP (2002). Detection of single molecules: solution-phase single-molecule fluorescence correlation spectroscopy as an ultrasensitive, rapid and reliable system for immunological investigation. J Immunol Methods 260 (1-2): 117-124.
17. Jermutus L, Kolly R, Földes-Papp Z, Hanes J, Rigler R, et al. (2002) Ligand binding of a ribosome-displayed protein detected in solution at the single molecule level by fluorescence correlation spectroscopy. Eur Biophys J 31 (3): 179-184.
18. Földes-Papp Z, Demel U, Tilz GP (2001) Ultrasensitive detection and identification of fluorescent molecules by FCS: impact for immunobiology. Proc Natl Acad Sci USA 98 (20): 11509-11514.
19. Stephan J, Dörre K, Brakmann S,Winkler T, Wetzel T, et al. (2001) Towards a general procedure for sequencing single DNA molecules. J Biotechnol 86 (3): 255-267.
20. Földes-Papp Z, Angerer B, Ankenbauer W, Rigler R (2001) Fluorescent high-density labeling of DNA: error-free substitution for a normal nucleotide. J Biotechnol 86 (3): 237-253.
21. Földes-Papp Z, Angerer B, Thyberg P, Hinz M, Wennmalm S, et al. (2001) Fluorescently labeled model DNA sequences for exonucleolytic sequencing. J Biotechnol 86 (3): 203-224.
22. Földes-Papp Z, Kinjo M (2001) Fluorescence correlation spectroscopy in nucleic acids analysis. In: Elson E, Rigler R, editors. Fluorescence correlation spectroscopy: theory and applications. Springer series in physical chemistry, vol 65. Boston: Springer. pp. 25-64.
23. Lagerkvist AC, Földes-Papp Z, Persson MA, Rigler R (2001) Fluorescence correlation spectroscopy as a method for assessment of interactions between phage displaying antibodies and soluble antigen. Protein Sci 10 (8): 1522-1528.
24. Földes-Papp Z, Rigler R (2001) Quantitative two-color fluorescence cross-correlation spectroscopy in the analysis of polymerase chain reaction. Biol Chem 382 (3): 473-478.
25. Bark N, Földes-Papp Z, Rigler R (1999) The incipient stage in thrombin-induced fibrin polymerization detected by FCS at the single molecule level. Biochem Biophys Res Commun 260 (1): 35-41.
26. Rigler R, Földes-Papp Z, Meyer-Almes FJ, Sammet C, Völcker M, et al. (1998) Fluorescence cross-correlation: a new concept for polymerase chain reaction. J Biotechnol 63 (2): 97-109.
27. Baumann G, Gryczynski I. Földes-Papp Z (2010) Anomalous behavior in length distributions of 3D random Brownian walks and measured photon count rates within observation volumes of single-molecule trajectories in fluorescence fluctuation microscopy. Optics Express 18 (17): 17883-17896.
28. Zustiak SP, Nossal R, Sackett DL (2011) Hindered diffusion in polymeric solutions studied by fluorescence correlation spectroscopy. Biophys J 101 (1): 255–264.
29. Braet C, Stephan H, Dobbie IM, Togashi DM, Ryder AG, et al. (2007) Mobility and distribution of replication protein A in living cells using fluorescence correlation spectroscopy. Exp Mol Pathol 82 (2): 156-162.
30. Feder TJ, Brust-Mascher I, Slattery JP, Baird B, Webb WW (1996) Constrained diffusion or immobile fraction of cell surfaces: a new interpretation. Biophys J 70: 2767-2773.
31. Schwille P, Haupts U, Maiti S, Webb WW (1999) Molecular dynamics in living cells observed by fluorescence correlation spectroscopy with one- and two-photon excitation. Biophys J 77: 2251-2265.
32. Wu J, Berland KM (2008) Propagators and time-dependent diffusion coefficients for anomalous diffusion. Biophys J 95: 2049-2052.
33. Dix JA, Verkman AS (2008) Crowding effects on diffusion in solution and cells. Annu Rev Biophys 37: 247-263.
34. Szymanski J, Weiss, W (2009) Elucidating the origin of anomalous diffusion in crowded fluids. Phys Rev Lett 103: 038102.
35. Földes-Papp Z (2006) What it means to measure a single molecule in a solution by fluorescence fluctuation spectroscopy. Ex Mol Pathol 80 (3): 209-218.
36. Földes-Papp Z (2007) ‘True’ single-molecule molecule observations by fluorescence correlation spectroscopy and two-color fluorescence cross-correlation spectroscopy. Exp Mol Pathol 82 (2): 147-155.
37. Meroz Y, Sokolov IM, Klafter J (2010) Subdiffusion of mixed origins: when ergodicity and nonergodicity coexist. Phys Rev E 81: 010101(R).
38. Sokolov IM (2012) Models of anomalous diffusion in crowded environments. Soft Matter 8: 9043–9052.
39. Weigel AV, Simon B, Tamkun MM, Krapf D (2011) Ergodic and nonergodic processes coexist in the plasma membrane as observed by single-molecule tracking. Proc Natl Acad Sci US.A 108 (16): 6438–6443.
40. Heitzer MD, Wolf IM, Sanchez ER, Witchel SF, DeFranco DB (2007) Glucocorticoid receptor physiology. Rev Endocr Metab Disord 8: 321-330.
41. Mikuni S, Tamura M, Kinjo M (2007) Analysis of intranuclear binding process of glucocorticoid receptor using fluorescence correlation spectroscopy. FEBS Lett 581: 389-393.
42. Cheung J, Smith F (2000) Molecular chaperone interactions with steroid receptors: an update. Mol Endocrinol 14: 939-946.
43. McNally JG, Muller WG, Walker D, Wolford R, Hager GL (2000) The glucocorticoid receptor: rapid exchange with regulatory sites in living cells. Science 287: 1262-1265.
44. De Bosscher K, Haegeman G (2009) Minireview: Latest perspectives on antiinflammatory actions of glucocorticoids. Mol Endocrinol 23: 281-291.
45. Vandevyver S, Dejager L, Libert C (2012) On the trail of the glucocorticoid receptor: into the nucleus and back. Traffic 13: 364-374.
46. Silverman MN, Mukhopadhyay P, Belyavskaya E, Tonelli LH, Revenis BD, et al. (2013) Glucocorticoid receptor dimerization is required for proper recovery of LPS-induced inflammation, sickness behavior and metabolism in mice. Mol Psychiatry 18 (9): 1006-1017.
47. Magde D, Elson E., Webb WW (1972) Thermodynamic fluctuations in a reacting system: measurement by fluorescence correlation spectroscopy. Phys Rev Lett 29: 705–708
48. Eigen M, Rigler R (1994) Sorting single molecules: application to diagnostics and evolutionary biotechnology. Proc Natl Acad Sci USA 91 (57): 40–47.
49. Barkai E, Metzler R, Klafter J (2000) From continuous time random walks to the fractional Fokker-Planck equation. Phys Rev E, 61: 132–138.
50. Metzler R, Klafter J (2000) The random walker's guide to anomalous diffusion: a fractal dynamics approach. Phys Rep 339: 1–77.
51. Havlin S, Ben-Avraham D (1987) Diffusion in disordered media. Adv Phys 36: 695–798.
52. Gebhardt JC, Suter DM, Roy R, Zhao ZW, Chapman AR, et al. (2013) Single-molecule imaging of transcription factor binding to DNA in live mammalian cells. Nat Methods 10 (5): 421-426.
53. Mazza D, Mueller F, Stasevich TJ, McNally JG (2013) Convergence of chromatin binding estimates in live cells. Nat Methods 10 (8): 691-692.
54. Kleiman A, Hübner S, Rodriguez Parkitna JM, Neumann A, Hofer S, et al. (2012) Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages. FASEB J 26 (2): 722-729.
55. Földes-Papp Z (2013) Measurements of single molecules in solution and live cells over longer observation times than those currently possible: the meaningful time. Curr Pharm Biotechnol 14 (4): 441-444.
56. Földes-Papp Z (2005) How the molecule number is correctly quantified in two-color fluorescence cross-correlation spectroscopy: corrections for cross-talk and quenching in experiments. Curr Pharm Biotechnol 6 ( 6): 437-444.
57. Földes-Papp Z (2007) Fluorescence fluctuation spectroscopic approaches to the study of a single molecule diffusing in solution and a live cell without systemic drift or convection: a theoretical study. Curr Pharm Biotechnol 8(5): 261-273.
58. Digman MA., Gratton E (2011) Lessons in fluctuation correlation spectroscopy. Annu Rev Phys Chem 62: 645-668.
59. Di Rienzo C, Gratton E, Beltram F, Cardarelli F (2013) Fast spatiotemporal correlation spectroscopy to determine protein lateral diffusion laws in live cell membranes. Proc Natl Acad Sci USA 110 (30): 12307-12312.
60. Digman MA, Gratton E (2009) Imaging barriers to diffusion by pair correlation functions. Biophys J 97: 665–673.
61. Cardarelli F, Gratton E (2010) In vivo imaging of single-molecule translocation through nuclear pore complexes by pair correlation functions. PLoS One 5 (5): e10475.
62 Földes-Papp Z (2002) Theory of measuring the selfsame single fluorescent molecule in solution suited for studying individual molecular interactions by SPSM-FCS Pteridines 13: 73-82.
63. Földes-Papp Z, Baumann G, Demel U, Tilz GP (2004) Counting and behavior of an individual fluorescent molecule without hydrodynamic flow, immobilization, or photon count statistics. Curr Pharm Biotechnol 5 (2): 163-172.
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Mar 15, 2014
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Baumann G, Kinjo M, Földes-Papp Z. Anomalous Subdiffusive Measurements by Fluorescence Correlations Spectroscopy and Simulations of Translational Diffusive Behavior in Live Cells. J Biol Methods [Internet]. 2014 Mar. 15 [cited 2024 Apr. 19];1(1):e3. Available from: https://jbmethods.org/index.php/jbm/article/view/17
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