Proceedings Article

Anti-Brownian ELectrokinetic (ABEL) trapping of single β2-adrenergic receptors in the absence and presence of agonist

[+] Author Affiliations
Samuel Bockenhauer, W. E. Moerner

Stanford Univ. (USA)

Alexandre Fuerstenberg

Stanford Univ. (USA) and Univ. of Geneva (Switzerland)

Xiao Jie Yao, Brian K. Kobilka

Stanford Univ. Medical School (USA)

Proc. SPIE 8228, Single Molecule Spectroscopy and Superresolution Imaging V, 822805 (February 9, 2012); doi:10.1117/12.910018
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Open Access

From Conference Volume 8228

  • Single Molecule Spectroscopy and Superresolution Imaging V
  • Jörg Enderlein; Zygmunt K. Gryczynski; Rainer Erdmann; Felix Koberling; Ingo Gregor
  • San Francisco, California, USA | January 21, 2012

abstract

The ABEL trap allows trapping of single biomolecules in solution for extended observation without immobilization. The essential idea combines fluorescence-based position estimation with fast electrokinetic feedback in a microfluidic geometry to counter the Brownian motion of a single nanoscale object, hence maintaining its position in the field of view for hundreds of milliseconds to seconds. Such prolonged observation of single proteins allows access to slow dynamics, as probed by any available photophysical observables. We have used the ABEL trap to study conformational dynamics of the β2-adrenergic receptor, a key G-protein coupled receptor and drug target, in the absence and presence of agonist. A single environment-sensitive dye reports on the receptor microenvironment, providing a real-time readout of conformational change for each trapped receptor. The focus of this paper will be a quantitative comparison of the ligandfree and agonist-bound receptor data from our ABEL trap experiments. We observe a small but clearly detectable shift in conformational equilibria and a lengthening of fluctuation timescales upon binding of agonist. In order to quantify the shift in state distributions and timescales, we apply nonparametric statistical tests to place error bounds on the resulting single-molecule distributions.

© (2012) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

references

Moerner, W. E., Kador, L. "Optical detection and spectroscopy of single molecules in a solid," Phys. Rev. Lett. 62, 2535-2538 (1989).10.1103/PhysRevLett.62.2535
Moerner, W. E. Single-Molecule Optical Spectroscopy and Imaging: From Early Steps to Recent Advances, Springer-Verlag, Berlin, 25-60 (2009).
Weiss, S. "Fluorescence Spectroscopy of Single Biomolecules," Science 283, 1676-1683 (1999).10.1126/science.283.5408.1676
Moerner, W. E. "New directions in single-molecule imaging and analysis," Proc. Natl. Acad. Sci. USA 104, 12596-12602 (2007).10.1073/pnas.0610081104
Cornish, P. V., Ha, T. "A Survey of Single-Molecule Techniques in Chemical Biology," ACS Chem. Biol. 2(1), 53 (2007).10.1021/cb600342a
Ashkin, A., Dziedzic, J. M., Bjorkholm, J. E. and Chu, S. "Observation of a single-beam gradient force optical trap for dielectric particles," Opt. Lett. 11, 288-290 (1986).10.1364/OL.11.000288
Cohen, A. E., Moerner, W. E. "Suppressing Brownian motion of individual biomolecules in solution," Proc. Natl. Acad. Sci. USA 103, 4362-4365 (2006).10.1073/pnas.0509976103
Cohen, A. E., Moerner, W. E. "Principal-components analysis of shape fluctuations of single DNA molecules," Proc. Natl. Acad. Sci. USA 104(31), 12622-12627 (2007).10.1073/pnas.0610396104
Cohen, A. E., Moerner, W. E. "Controlling Brownian motion of single protein molecules and single fluorophores in aqueous buffer," Opt. Express 16, 6941-6956 (2008).10.1364/OE.16.006941
Goldsmith, R. H., Moerner, W. E. "Watching conformational- and photodynamics of single fluorescent proteins in solution," Nat. Chem. 2(3), 179-186 (2010).10.1038/nchem.545
Fields, A. P., Cohen, A. E. "Anti-Brownian traps for studies on single molecules," Methods Enzymol. 475, 149-174 (2010).10.1016/S0076-6879(10)75007-2
Wang, Q., Moerner, W. E. "An adaptive Anti-Brownian ELectrokinetic (ABEL) trap with real-time information on single-molecule diffusivity and mobility," ACS Nano 5, 5792-5799 (2011).10.1021/nn2014968
Fields, A. P., Cohen, A. E. "Electrokinetic trapping at the one nanometer limit," Proc. Natl. Acad. Sci. USA 108, 8937-8942 (2011).10.1073/pnas.1103554108
Goldsmith, R. H., Tabares, L. C., Kostrz, D., Dennison, C., Aartsma, T. J., Canters, G. W. and Moerner, W. E. "Redox cycling and kinetic analysis of single molecules of solution-phase nitrite reductase," Proc. Natl. Acad. Sci. USA early edition, 17274 (2011).
Jiang, Y., Douglas, N. R., Conley, N. R., Miller, E. J., Frydman, J. and Moerner, W. E. "Sensing cooperativity in ATP hydrolysis for single multisubunit enzymes in solution," Proc. Natl. Acad. Sci. USA 108, 16962-16967 (2011).10.1073/pnas.1112244108
Bockenhauer, S., Fuerstenberg, A., Yao, J. Y., Kobilka, B. K. and Moerner, W. E. "Conformational dynamics of single G protein-coupled receptors in solution," J. Phys. Chem. B 115, 13328-13338 (2011).10.1021/jp204843r
Frauenfelder, H., Parak, F. and Young, R. D. "Conformational substates in proteins," Annu. Rev. Biophys. Biophys. Chem. 17, 451-479 (1988).10.1146/annurev.bb.17.060188.002315
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Kenakin, T. P. "Cellular assays as portals to seven-transmembrane receptor-based drug discovery," Nat. Rev. Drug Discov. 8(8), 617-626 (2009).10.1038/nrd2838
Park, P. S. H., Lodowski, D. T. and Palczewski, K. "Activation of G protein-coupled receptors: Beyond two-state models and tertiary conformational changes," Annu. Rev. Pharmacol. Toxicol. 48, 107-141 (2008).10.1146/annurev.pharmtox.48.113006.094630
Vilardaga, J. P., Steinmeyer, R., Harms, G. S. and Lohse, M. J. "Molecular basis of inverse agonism in a G protein-coupled receptor," Nat. Chem. Biol. 1(1), 25-28 (2005).10.1038/nchembio705
Swaminath, G., Xiang, Y., Lee, T. W., Steenhuis, J. J., Parnot, C. and Kobilka, B. K. "Sequential binding of agonists to the beta-2-adrenoreceptor," J. Biol. Chem. 279, 686-691 (2004).
Gaertner, H., Cerini, F., Escola, J., Kuenzi, G., Melotti, A., Offord, R., Rossitto-Borlat, I., Nedellec, R., Salkowitz, J., Gorochov, G., Mosier, D. and Hartley, O. "Highly potent, fully recombinant anti-HIV chemokines: reengineering a low-cost microbicide," Proc. Natl. Acad. Sci. USA 105(46), 17706-17711 (2008).10.1073/pnas.0805098105
Vilardaga, J. P., Bünemann, M., Krasel, C., Castro, M. and Lohse, M. J. "Measurement of the millisecond activation switch of G protein-coupled receptors in living cells," Nature Biotech. 21, 807-812 (2003).10.1038/nbt838
Rasmussen, S. G. F., Choi, H., Fung, J. J., Pardon, E., Casarosa, P., Chae, P. S., DeVree, B. T., Rosenbaum, D. M., Thian, F. S., Kobilka, T. S., Schnapp, A., Konetzki, I., Sunahara, R. K., Gellman, S. H., Pautsch, A., Steyaert, J., Weis, W. I. and Kobilka, B. K. "Structure of a nanobody-stabilized active state of the beta 2 adrenoceptor," Nature 469(7329), 175-180 (2011).10.1038/nature09648
Rosenbaum, D. M., Zhang, C., Lyons, J. A., Holl, R., Aragao, D., Arlow, D. H., Rasmussen, S. G. F., Choi, H., DeVree, B. T., Sunahara, R. K., Chae, P. S., Gellman, S. H., Dror, R. O., Shaw, D. E., Weis, W. I., Caffrey, M., Gmeiner, P. and Kobilka, B. K. "Structure and function of an irreversible agonist-beta 2 adrenoceptor complex," Nature 469(7329), 236-240 (2011).10.1038/nature09665
Warne, T., Moukhametzianov, R., Baker, J. G., Nehme, R., Edwards, P. C., Leslie, A. G. W., Schertler, G. F. X. and Tate, C. G. "The structural basis for agonist and partial agonist action on a beta 1-adrenergic receptor," Nature 469(7329), 241-244 (2011).10.1038/nature09746
Blanpain, C., Vanderwinden, J. M., Cihak, J., Wittamer, V., Le Poul, E., Issafras, H., Stangassinger, M., Vassart, G., Marullo, S., Schlöndorff, D., Parmentier, M. and Mack, M. "Mulitple active states and oligomerization of CCR5 revealed by functional properties of monoclonal antibodies," Mol. Biol. Cell 13, 723-737 (2002).10.1091/mbc.01-03-0129
Ghanouni, P., Steenhuis, J. J., Farrens, D. L. and Kobilka, B. K. "Agonist-induced conformational changes in the G-protein-coupling domain of the beta-2-adrenergic receptor," Proc. Natl. Acad. Sci. USA 98, 5997-6002 (2001).10.1073/pnas.101126198
Yao, X. J., Ruiz, G. V., Whorton, M. R., Rasmussen, S. G. F., DeVree, B. T., Deupi, X., Sunahara, R. K. and Kobilka, B. "The effect of ligand efficacy on the formation and stability of a GPCR-G protein complex," Proc. Natl. Acad. Sci. USA 106(23), 9501-9506, S9501/1-S9501/3 (2009).
Cohen, A. E., Moerner, W. E. "The Anti-Brownian ELectrophoretic trap (ABEL trap): fabrication and software," Proc. SPIE 5699, 296-305 (2005).10.1117/12.598689
Jiang, Y., Wang, Q., Cohen, A. E., Douglas, N., Frydman, J. and Moerner, W. E. "Hardware-based anti-Brownian electrokinetic trap (ABEL trap) for single molecules: control loop simulations and application to ATP binding stoichiometry in multi-subunit enzymes," Proc Soc Photo Opt Instrum Eng. 7038, 703807 (2008).
Yao, X. J., Parnot, C., Deupi, X., Ratnala, V. R. P., Swaminath, G., Farrens, D. and Kobilka, B. "Coupling ligand structure to specific conformational switches in the beta(2)-adrenoceptor," Nat. Chem. Biol. 2(8), 417-422 (2006).10.1038/nchembio801
Watkins, L. P., Yang, H. "Detection of intensity change points in time-resolved single-molecule measurements," J. Phys. Chem. B 109, 617-628 (2005).10.1021/jp0467548
Zander, C., Sauer, M., Drexhage, K. H., Ko, D. S., Schulz, A., Wolfrum, J., Brand, L., Eggeling, C. and Seidel, C. A. M. "Detection and characterization of single molecules in aqueous solution," Appl. Phy. B 63, 517-523 (1996).
Schwille, P., Kummer, S., Heikal, A. A., Moerner, W. E. and Webb, W. W. "Fluorescence Correlation Spectroscopy Reveals Fast Optical Excitation-Driven Intermolecular Dynamics of Yellow Fluorescent Proteins," Proc. Natl. Acad. Sci. USA 97, 151-156 (2000).10.1073/pnas.97.1.151
Chung, S. H., Stevens, J. R. "Time-dependent correlation and the evaluation of the stretched exponential or Kohlrausch-Williams-Watts function," Amer. J. Phys. 59, 1024-1030 (1991).10.1119/1.16640
Lu, C. Y., VandenBout, D. A. "Effect of finite trajectory length on the correlation function analysis of single molecule data," J. Chem. Phys. 125, 124701-1-124701-9 (2006).10.1063/1.2352748
Massey, F. J. "The Kolmogorov-Smirnov Test for Goodness of Fit," Journal of the American Statistical Association 46, 251, 68-78 (1951).10.2307/2280095
Efron, B., Tibshirani, R. An Introduction to the Bootstrap, Chapman & Hall, New York City, (1993).
Thompson, M. A., Casolari, J. M., Badieirostami, M., Brown, P. O. and Moerner, W. E. "Three-dimensional tracking of single mRNA particles in Saccharomyces cerevisiae using a double-helix point spread function," Proc. Natl. Acad. Sci. USA 107, 17864-17871 (2010).10.1073/pnas.1012868107
Lakowicz, J. R. Principles of fluorescence spectroscopy, Springer Science, New York, 954 (2006).10.1007/978-0-387-46312-4
Frauenfelder, H., et al. "A Unified Model of Protein Dynamics," PNAS 106, 5129 (2009).10.1073/pnas.0900336106
Kou, S. C., Xie, X. S. "Generalized Langevin Equation with Fractional Gaussian Noise: Subdiffusion within a Single Protein Molecule," Phys. Rev. Letters 93, 180603 (2004).10.1103/PhysRevLett.93.180603
Watanabe, K., Klein, M. L. "Shape fluctuations in ionic micelles," J. Phys. Chem. 93(19), 6897-6901 (1989).10.1021/j100356a006
Halle, B., Landgren, M. and Jonsson, B. "The shape of ionic micelles," Journal de Physique 49(7), 1235-1259 (1988).10.1051/jphys:019880049070123500
Bond, P. J., Cuthbertson, J. M., Deol, S. S. and Sansom, M. S. P. "MD simulations of spontaneous membrane protein/detergent micelle formation," J. Am. Chem. Soc. 126(49), 15948-15949 (2004).10.1021/ja044819e
Full text of this article:
Citation

Samuel Bockenhauer ; Alexandre Fuerstenberg ; Xiao Jie Yao ; Brian K. Kobilka and W. E. Moerner
"Anti-Brownian ELectrokinetic (ABEL) trapping of single β2-adrenergic receptors in the absence and presence of agonist", Proc. SPIE 8228, Single Molecule Spectroscopy and Superresolution Imaging V, 822805 (February 9, 2012); doi:10.1117/12.910018; http://dx.doi.org/10.1117/12.910018


Figures

Tables

Moerner, W. E., Kador, L. "Optical detection and spectroscopy of single molecules in a solid," Phys. Rev. Lett. 62, 2535-2538 (1989).10.1103/PhysRevLett.62.2535
Moerner, W. E. Single-Molecule Optical Spectroscopy and Imaging: From Early Steps to Recent Advances, Springer-Verlag, Berlin, 25-60 (2009).
Weiss, S. "Fluorescence Spectroscopy of Single Biomolecules," Science 283, 1676-1683 (1999).10.1126/science.283.5408.1676
Moerner, W. E. "New directions in single-molecule imaging and analysis," Proc. Natl. Acad. Sci. USA 104, 12596-12602 (2007).10.1073/pnas.0610081104
Cornish, P. V., Ha, T. "A Survey of Single-Molecule Techniques in Chemical Biology," ACS Chem. Biol. 2(1), 53 (2007).10.1021/cb600342a
Ashkin, A., Dziedzic, J. M., Bjorkholm, J. E. and Chu, S. "Observation of a single-beam gradient force optical trap for dielectric particles," Opt. Lett. 11, 288-290 (1986).10.1364/OL.11.000288
Cohen, A. E., Moerner, W. E. "Suppressing Brownian motion of individual biomolecules in solution," Proc. Natl. Acad. Sci. USA 103, 4362-4365 (2006).10.1073/pnas.0509976103
Cohen, A. E., Moerner, W. E. "Principal-components analysis of shape fluctuations of single DNA molecules," Proc. Natl. Acad. Sci. USA 104(31), 12622-12627 (2007).10.1073/pnas.0610396104
Cohen, A. E., Moerner, W. E. "Controlling Brownian motion of single protein molecules and single fluorophores in aqueous buffer," Opt. Express 16, 6941-6956 (2008).10.1364/OE.16.006941
Goldsmith, R. H., Moerner, W. E. "Watching conformational- and photodynamics of single fluorescent proteins in solution," Nat. Chem. 2(3), 179-186 (2010).10.1038/nchem.545
Fields, A. P., Cohen, A. E. "Anti-Brownian traps for studies on single molecules," Methods Enzymol. 475, 149-174 (2010).10.1016/S0076-6879(10)75007-2
Wang, Q., Moerner, W. E. "An adaptive Anti-Brownian ELectrokinetic (ABEL) trap with real-time information on single-molecule diffusivity and mobility," ACS Nano 5, 5792-5799 (2011).10.1021/nn2014968
Fields, A. P., Cohen, A. E. "Electrokinetic trapping at the one nanometer limit," Proc. Natl. Acad. Sci. USA 108, 8937-8942 (2011).10.1073/pnas.1103554108
Goldsmith, R. H., Tabares, L. C., Kostrz, D., Dennison, C., Aartsma, T. J., Canters, G. W. and Moerner, W. E. "Redox cycling and kinetic analysis of single molecules of solution-phase nitrite reductase," Proc. Natl. Acad. Sci. USA early edition, 17274 (2011).
Jiang, Y., Douglas, N. R., Conley, N. R., Miller, E. J., Frydman, J. and Moerner, W. E. "Sensing cooperativity in ATP hydrolysis for single multisubunit enzymes in solution," Proc. Natl. Acad. Sci. USA 108, 16962-16967 (2011).10.1073/pnas.1112244108
Bockenhauer, S., Fuerstenberg, A., Yao, J. Y., Kobilka, B. K. and Moerner, W. E. "Conformational dynamics of single G protein-coupled receptors in solution," J. Phys. Chem. B 115, 13328-13338 (2011).10.1021/jp204843r
Frauenfelder, H., Parak, F. and Young, R. D. "Conformational substates in proteins," Annu. Rev. Biophys. Biophys. Chem. 17, 451-479 (1988).10.1146/annurev.bb.17.060188.002315
Henzler-Wildman, K., Kern, D. "Dynamic personalities of proteins," Nature 450(7172), 964-972 (2007).10.1038/nature06522
Kenakin, T. P. "Cellular assays as portals to seven-transmembrane receptor-based drug discovery," Nat. Rev. Drug Discov. 8(8), 617-626 (2009).10.1038/nrd2838
Park, P. S. H., Lodowski, D. T. and Palczewski, K. "Activation of G protein-coupled receptors: Beyond two-state models and tertiary conformational changes," Annu. Rev. Pharmacol. Toxicol. 48, 107-141 (2008).10.1146/annurev.pharmtox.48.113006.094630
Vilardaga, J. P., Steinmeyer, R., Harms, G. S. and Lohse, M. J. "Molecular basis of inverse agonism in a G protein-coupled receptor," Nat. Chem. Biol. 1(1), 25-28 (2005).10.1038/nchembio705
Swaminath, G., Xiang, Y., Lee, T. W., Steenhuis, J. J., Parnot, C. and Kobilka, B. K. "Sequential binding of agonists to the beta-2-adrenoreceptor," J. Biol. Chem. 279, 686-691 (2004).
Gaertner, H., Cerini, F., Escola, J., Kuenzi, G., Melotti, A., Offord, R., Rossitto-Borlat, I., Nedellec, R., Salkowitz, J., Gorochov, G., Mosier, D. and Hartley, O. "Highly potent, fully recombinant anti-HIV chemokines: reengineering a low-cost microbicide," Proc. Natl. Acad. Sci. USA 105(46), 17706-17711 (2008).10.1073/pnas.0805098105
Vilardaga, J. P., Bünemann, M., Krasel, C., Castro, M. and Lohse, M. J. "Measurement of the millisecond activation switch of G protein-coupled receptors in living cells," Nature Biotech. 21, 807-812 (2003).10.1038/nbt838
Rasmussen, S. G. F., Choi, H., Fung, J. J., Pardon, E., Casarosa, P., Chae, P. S., DeVree, B. T., Rosenbaum, D. M., Thian, F. S., Kobilka, T. S., Schnapp, A., Konetzki, I., Sunahara, R. K., Gellman, S. H., Pautsch, A., Steyaert, J., Weis, W. I. and Kobilka, B. K. "Structure of a nanobody-stabilized active state of the beta 2 adrenoceptor," Nature 469(7329), 175-180 (2011).10.1038/nature09648
Rosenbaum, D. M., Zhang, C., Lyons, J. A., Holl, R., Aragao, D., Arlow, D. H., Rasmussen, S. G. F., Choi, H., DeVree, B. T., Sunahara, R. K., Chae, P. S., Gellman, S. H., Dror, R. O., Shaw, D. E., Weis, W. I., Caffrey, M., Gmeiner, P. and Kobilka, B. K. "Structure and function of an irreversible agonist-beta 2 adrenoceptor complex," Nature 469(7329), 236-240 (2011).10.1038/nature09665
Warne, T., Moukhametzianov, R., Baker, J. G., Nehme, R., Edwards, P. C., Leslie, A. G. W., Schertler, G. F. X. and Tate, C. G. "The structural basis for agonist and partial agonist action on a beta 1-adrenergic receptor," Nature 469(7329), 241-244 (2011).10.1038/nature09746
Blanpain, C., Vanderwinden, J. M., Cihak, J., Wittamer, V., Le Poul, E., Issafras, H., Stangassinger, M., Vassart, G., Marullo, S., Schlöndorff, D., Parmentier, M. and Mack, M. "Mulitple active states and oligomerization of CCR5 revealed by functional properties of monoclonal antibodies," Mol. Biol. Cell 13, 723-737 (2002).10.1091/mbc.01-03-0129
Ghanouni, P., Steenhuis, J. J., Farrens, D. L. and Kobilka, B. K. "Agonist-induced conformational changes in the G-protein-coupling domain of the beta-2-adrenergic receptor," Proc. Natl. Acad. Sci. USA 98, 5997-6002 (2001).10.1073/pnas.101126198
Yao, X. J., Ruiz, G. V., Whorton, M. R., Rasmussen, S. G. F., DeVree, B. T., Deupi, X., Sunahara, R. K. and Kobilka, B. "The effect of ligand efficacy on the formation and stability of a GPCR-G protein complex," Proc. Natl. Acad. Sci. USA 106(23), 9501-9506, S9501/1-S9501/3 (2009).
Cohen, A. E., Moerner, W. E. "The Anti-Brownian ELectrophoretic trap (ABEL trap): fabrication and software," Proc. SPIE 5699, 296-305 (2005).10.1117/12.598689
Jiang, Y., Wang, Q., Cohen, A. E., Douglas, N., Frydman, J. and Moerner, W. E. "Hardware-based anti-Brownian electrokinetic trap (ABEL trap) for single molecules: control loop simulations and application to ATP binding stoichiometry in multi-subunit enzymes," Proc Soc Photo Opt Instrum Eng. 7038, 703807 (2008).
Yao, X. J., Parnot, C., Deupi, X., Ratnala, V. R. P., Swaminath, G., Farrens, D. and Kobilka, B. "Coupling ligand structure to specific conformational switches in the beta(2)-adrenoceptor," Nat. Chem. Biol. 2(8), 417-422 (2006).10.1038/nchembio801
Watkins, L. P., Yang, H. "Detection of intensity change points in time-resolved single-molecule measurements," J. Phys. Chem. B 109, 617-628 (2005).10.1021/jp0467548
Zander, C., Sauer, M., Drexhage, K. H., Ko, D. S., Schulz, A., Wolfrum, J., Brand, L., Eggeling, C. and Seidel, C. A. M. "Detection and characterization of single molecules in aqueous solution," Appl. Phy. B 63, 517-523 (1996).
Schwille, P., Kummer, S., Heikal, A. A., Moerner, W. E. and Webb, W. W. "Fluorescence Correlation Spectroscopy Reveals Fast Optical Excitation-Driven Intermolecular Dynamics of Yellow Fluorescent Proteins," Proc. Natl. Acad. Sci. USA 97, 151-156 (2000).10.1073/pnas.97.1.151
Chung, S. H., Stevens, J. R. "Time-dependent correlation and the evaluation of the stretched exponential or Kohlrausch-Williams-Watts function," Amer. J. Phys. 59, 1024-1030 (1991).10.1119/1.16640
Lu, C. Y., VandenBout, D. A. "Effect of finite trajectory length on the correlation function analysis of single molecule data," J. Chem. Phys. 125, 124701-1-124701-9 (2006).10.1063/1.2352748
Massey, F. J. "The Kolmogorov-Smirnov Test for Goodness of Fit," Journal of the American Statistical Association 46, 251, 68-78 (1951).10.2307/2280095
Efron, B., Tibshirani, R. An Introduction to the Bootstrap, Chapman & Hall, New York City, (1993).
Thompson, M. A., Casolari, J. M., Badieirostami, M., Brown, P. O. and Moerner, W. E. "Three-dimensional tracking of single mRNA particles in Saccharomyces cerevisiae using a double-helix point spread function," Proc. Natl. Acad. Sci. USA 107, 17864-17871 (2010).10.1073/pnas.1012868107
Lakowicz, J. R. Principles of fluorescence spectroscopy, Springer Science, New York, 954 (2006).10.1007/978-0-387-46312-4
Frauenfelder, H., et al. "A Unified Model of Protein Dynamics," PNAS 106, 5129 (2009).10.1073/pnas.0900336106
Kou, S. C., Xie, X. S. "Generalized Langevin Equation with Fractional Gaussian Noise: Subdiffusion within a Single Protein Molecule," Phys. Rev. Letters 93, 180603 (2004).10.1103/PhysRevLett.93.180603
Watanabe, K., Klein, M. L. "Shape fluctuations in ionic micelles," J. Phys. Chem. 93(19), 6897-6901 (1989).10.1021/j100356a006
Halle, B., Landgren, M. and Jonsson, B. "The shape of ionic micelles," Journal de Physique 49(7), 1235-1259 (1988).10.1051/jphys:019880049070123500
Bond, P. J., Cuthbertson, J. M., Deol, S. S. and Sansom, M. S. P. "MD simulations of spontaneous membrane protein/detergent micelle formation," J. Am. Chem. Soc. 126(49), 15948-15949 (2004).10.1021/ja044819e
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