Recent Advances in Single-Molecule Tracking and Imaging Techniques

Literature Cited

1. 1.

   Dovichi NJ, Martin JC, Jett JH, Trkula M, Keller RA. 1984. Laser-induced fluorescence of flowing samples as an approach to single-molecule detection in liquids. Anal. Chem. 56:348–54
   [Google Scholar]
2. 2.

   Peck K, Stryer L, Glazer AN, Mathies RA. 1989. Single-molecule fluorescence detection—auto-correlation criterion and experimental realization with phycoerythrin. PNAS 86:4087–91
   [Google Scholar]
3. 3.

   Keller RA, Ambrose WP, Goodwin PM, Jett JH, Martin JC, Wu M. 1996. Single-molecule fluorescence analysis in solution. Appl. Spectrosc. 50:12A–32A
   [Google Scholar]
4. 4.

   Shera EB, Seitzinger NK, Davis LM, Keller RA, Soper SA. 1990. Detection of single fluorescent molecules. Chem. Phys. Lett. 174:553–57
   [Google Scholar]
5. 5.

   Soper SA, Shera EB, Martin JC, Jett JH, Hahn JH et al. 1991. Single-molecule detection of Rhodamine 6G in ethanolic solutions using continuous wave laser excitation. Anal. Chem. 63:432–37
   [Google Scholar]
6. 6.

   Soper SA, Davis LM, Shera EB. 1992. Detection and identification of single molecules in solution. JOSA B 9:1761–69
   [Google Scholar]
7. 7.

   Ambrose WP, Goodwin PM, Jett JH, Van Orden A, Werner JH, Keller RA. 1999. Single molecule fluorescence spectroscopy at ambient temperature. Chem. Rev. 99:2929–56
   [Google Scholar]
8. 8.

   Zander C, Enderlein J, Keller RA. 2002. Single Molecule Detection in Solution: Methods and Applications Berlin/New York: Wiley-VHC
9. 9.

   Moerner WE. 2002. A dozen years of single-molecule spectroscopy in physics, chemistry, and biophysics. J. Phys. Chem. B 106:910–27
   [Google Scholar]
10. 10.

    Moerner W, Shechtman Y, Wang Q. 2015. Single-molecule spectroscopy and imaging over the decades. Faraday Discuss 184:9–36
    [Google Scholar]
11. 11.

    Chen Y-I, Chang Y-J, Nguyen TD, Liu C, Phillion S et al. 2019. Measuring DNA hybridization kinetics in live cells using a time-resolved 3D single-molecule tracking method. J. Am. Chem. Soc. 141:15747–50
    [Google Scholar]
12. 12.

    Kasai RS, Kusumi A. 2014. Single-molecule imaging revealed dynamic GPCR dimerization. Curr. Opin. Cell Biol. 27:78–86
    [Google Scholar]
13. 13.

    Kasai RS, Suzuki KG, Prossnitz ER, Koyama-Honda I, Nakada C et al. 2011. Full characterization of GPCR monomer–dimer dynamic equilibrium by single molecule imaging. J. Cell Biol. 192:463–80
    [Google Scholar]
14. 14.

    Fujiwara T, Ritchie K, Murakoshi H, Jacobson K, Kusumi A. 2002. Phospholipids undergo hop diffusion in compartmentalized cell membrane. J. Cell Biol. 157:1071–82
    [Google Scholar]
15. 15.

    Kim M, Hong S, Yankeelov TE, Yeh H-C, Liu Y-L. 2022. Deep learning-based classification of breast cancer cells using transmembrane receptor dynamics. Bioinformatics 38:243–49
    [Google Scholar]
16. 16.

    Khater IM, Nabi IR, Hamarneh G 2020. A review of super-resolution single-molecule localization microscopy cluster analysis and quantification methods. Patterns 1:100038
    [Google Scholar]
17. 17.

    Liu Y-L, Chou C-K, Kim M, Vasisht R, Kuo Y-A et al. 2019. Assessing metastatic potential of breast cancer cells based on EGFR dynamics. Sci. Rep. 9:3395
    [Google Scholar]
18. 18.

    Liu Y-L, Horning AM, Lieberman B, Lin C-K, Huang C-N et al. 2019. Spatial EGFR dynamics and metastatic phenotypes modulated by upregulated EPHB2 and SRC pathways predicting poor prognosis. Cancers 11:1910
    [Google Scholar]
19. 19.

    Lowe AR, Siegel JJ, Kalab P, Siu M, Weis K, Liphardt JT. 2010. Selectivity mechanism of the nuclear pore complex characterized by single cargo tracking. Nature 467:600–3
    [Google Scholar]
20. 20.

    Möller J, Isbilir A, Sungkaworn T, Osberg B, Karathanasis C et al. 2020. Single-molecule analysis reveals agonist-specific dimer formation of μ-opioid receptors. Nat. Chem. Biol. 16:946–54
    [Google Scholar]
21. 21.

    Perillo E, Liu Y-L, Huynh K, Liu C, Chou C-K et al. 2015. Deep and high-resolution 3D tracking of single particles using nonlinear and multiplexed illumination. Nat. Commun. 6:7874
    [Google Scholar]
22. 22.

    Liu Y-L, Perillo EP, Liu C, Yu P, Chou C-K et al. 2016. Segmentation of 3D trajectories acquired by TSUNAMI microscope: an application to EGFR trafficking. Biophys. J. 111:2214–27
    [Google Scholar]
23. 23.

    Liu C, Obliosca JM, Liu YL, Chen YA, Jiang N, Yeh HC. 2017. 3D single-molecule tracking enables direct hybridization kinetics measurement in solution. Nanoscale 9:5664–70
    [Google Scholar]
24. 24.

    Li CW, Lim SO, Chung EM, Kim YS, Park AH et al. 2018. Eradication of triple-negative breast cancer cells by targeting glycosylated PD-L1. Cancer Cell 33:187–201
    [Google Scholar]
25. 25.

    Liu Y-L, Perillo EP, Ang P, Kim M, Nguyen DT et al. 2020. Three-dimensional two-color dual-particle tracking microscope for monitoring DNA conformational changes and nanoparticle landings on live cells. ACS Nano 14:7927–39
    [Google Scholar]
26. 26.

    Tsunoyama TA, Watanabe Y, Goto J, Naito K, Kasai RS et al. 2018. Super-long single-molecule tracking reveals dynamic-anchorage-induced integrin function. Nat. Chem. Biol. 14:497–506
    [Google Scholar]
27. 27.

    Kusumi A, Tsunoyama TA, Hirosawa KM, Kasai RS, Fujiwara TK. 2014. Tracking single molecules at work in living cells. Nat. Chem. Biol. 10:524–32
    [Google Scholar]
28. 28.

    Deschout H, Zanacchi FC, Mlodzianoski M, Diaspro A, Bewersdorf J et al. 2014. Precisely and accurately localizing single emitters in fluorescence microscopy. Nat. Methods 11:253–66
    [Google Scholar]
29. 29.

    Liu Z, Lavis LD, Betzig E. 2015. Imaging live-cell dynamics and structure at the single-molecule level. Mol. Cell 58:644–59
    [Google Scholar]
30. 30.

    Liu C, Liu Y-L, Perillo EP, Dunn AK, Yeh H-C. 2016. Single-molecule tracking and its application in biomolecular binding detection. IEEE J. Sel. Top. Quantum Electron. 22:6804013
    [Google Scholar]
31. 31.

    von Diezmann A, Shechtman Y, Moerner WE. 2017. Three-dimensional localization of single molecules for super resolution imaging and single-particle tracking. Chem. Rev. 117:7244–75
    [Google Scholar]
32. 32.

    Shen H, Tauzin LJ, Baiyasi R, Wang WX, Moringo N et al. 2017. Single particle tracking: from theory to biophysical applications. Chem. Rev. 117:7331–76
    [Google Scholar]
33. 33.

    Lelek M, Gyparaki MT, Beliu G, Schueder F, Griffié J et al. 2021. Single-molecule localization microscopy. Nat. Rev. Methods Primers 1:39
    [Google Scholar]
34. 34.

    Yildiz A, Forkey JN, McKinney SA, Ha T, Goldman YE, Selvin PR. 2003. Myosin V walks hand-over-hand: single fluorophore imaging with 1.5-nm localization. Science 300:2061–65
    [Google Scholar]
35. 35.

    Coleman RA, Liu Z, Darzacq X, Tjian R, Singer RH, Lionnet T. 2016. Imaging transcription: past, present, and future. Cold Spring Harb. Symp. Quant. Biol. 80:1–8
    [Google Scholar]
36. 36.

    Chen H, Larson DR. 2016. What have single-molecule studies taught us about gene expression?. Genes Dev 30:1796–810
    [Google Scholar]
37. 37.

    Murakoshi H, Iino R, Kobayashi T, Fujiwara T, Ohshima C et al. 2004. Single-molecule imaging analysis of Ras activation in living cells. PNAS 101:7317–22
    [Google Scholar]
38. 38.

    Suzuki KGN, Kasai RS, Hirosawa KM, Nemoto YL, Ishibashi M et al. 2012. Transient GPI-anchored protein homodimers are units for raft organization and function. Nat. Chem. Biol. 8:774–83
    [Google Scholar]
39. 39.

    Benke A, Olivier N, Gunzenhauser J, Manley S. 2012. Multicolor single molecule tracking of stochastically active synthetic dyes. Nano Lett 12:2619–24
    [Google Scholar]
40. 40.

    Chen Z, Cao Y, Lin C-W, Alvarez S, Oh D et al. 2021. Nanopore-mediated protein delivery enabling three-color single-molecule tracking in living cells. PNAS 118:e2012229118
    [Google Scholar]
41. 41.

    Fujiwara TK, Takeuchi S, Kalay Z, Nagai Y, Tsunoyama TA et al. 2021. Development of ultrafast camera-based imaging of single fluorescent molecules and live-cell PALM. bioRxiv 465864. https://doi.org/10.1101/2021.10.26.465864
    [Crossref]
42. 42.

    Welsher K, Yang H. 2014. Multi-resolution 3D visualization of the early stages of cellular uptake of peptide-coated nanoparticles. Nat. Nanotechnol. 9:198–203
    [Google Scholar]
43. 43.

    Hirschfeld T. 1976. Optical microscopic observation of single small molecules. Appl. Opt. 15:2965–66
    [Google Scholar]
44. 44.

    Raj A, van den Bogaard P, Rifkin SA, van Oudenaarden A, Tyagi S. 2008. Imaging individual mRNA molecules using multiple singly labeled probes. Nat. Methods 5:877–79
    [Google Scholar]
45. 45.

    Tanenbaum ME, Gilbert LA, Qi LS, Weissman JS, Vale RD. 2014. A protein-tagging system for signal amplification in gene expression and fluorescence imaging. Cell 159:635–46
    [Google Scholar]
46. 46.

    Ghosh RP, Franklin JM, Draper WE, Shi Q, Beltran B et al. 2019. A fluorogenic array for temporally unlimited single-molecule tracking. Nat. Chem. Biol. 15:401–9
    [Google Scholar]
47. 47.

    Presman DM, Ball DA, Paakinaho V, Grimm JB, Lavis LD et al. 2017. Quantifying transcription factor binding dynamics at the single-molecule level in live cells. Methods 123:76–88
    [Google Scholar]
48. 48.

    Obliosca JM, Babin MC, Liu C, Liu Y-L, Chen Y-A et al. 2014. A complementary palette of NanoCluster beacons. ACS Nano 8:10150–60
    [Google Scholar]
49. 49.

    Grimm JB, Tkachuk AN, Xie L, Choi H, Mohar B et al. 2020. A general method to optimize and functionalize red-shifted rhodamine dyes. Nat. Methods 17:815–21
    [Google Scholar]
50. 50.

    Kuo Y-A, Jung C, Chen Y-A, Kuo H-C, Zhao OS et al. 2022. Massively parallel selection of nanocluster beacons. Adv. Mater. 34:2204957
    [Google Scholar]
51. 51.

    Frei MS, Tarnawski M, Roberti MJ, Koch B, Hiblot J, Johnsson K. 2022. Engineered HaloTag variants for fluorescence lifetime multiplexing. Nat. Methods 19:65–70
    [Google Scholar]
52. 52.

    Lippincott-Schwartz J, Patterson GH. 2009. Photoactivatable fluorescent proteins for diffraction-limited and super-resolution imaging. Trends Cell Biol 19:555–65
    [Google Scholar]
53. 53.

    Lang K, Chin JW. 2014. Cellular incorporation of unnatural amino acids and bioorthogonal labeling of proteins. Chem. Rev. 114:4764–806
    [Google Scholar]
54. 54.

    Li H, Vaughan JC. 2018. Switchable fluorophores for single-molecule localization microscopy. Chem. Rev. 118:9412–54
    [Google Scholar]
55. 55.

    Elf J, Li G-W, Xie XS. 2007. Probing transcription factor dynamics at the single-molecule level in a living cell. Science 316:1191–94
    [Google Scholar]
56. 56.

    Gebhardt JCM, 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 10:421–26
    [Google Scholar]
57. 57.

    Klein T, Proppert S, Sauer M. 2014. Eight years of single-molecule localization microscopy. Histochem. Cell Biol. 141:561–75
    [Google Scholar]
58. 58.

    Speil J, Baumgart E, Siebrasse J-P, Veith R, Vinkemeier U, Kubitscheck U. 2011. Activated STAT1 transcription factors conduct distinct saltatory movements in the cell nucleus. Biophys. J. 101:2592–600
    [Google Scholar]
59. 59.

    Dahan M, Levi S, Luccardini C, Rostaing P, Riveau B, Triller A. 2003. Diffusion dynamics of glycine receptors revealed by single-quantum dot tracking. Science 302:442–45
    [Google Scholar]
60. 60.

    Cai E, Ge PH, Lee SH, Jeyifous O, Wang Y et al. 2014. Stable small quantum dots for synaptic receptor tracking on live neurons. Angew. Chem. Int. Edit. 53:12484–88
    [Google Scholar]
61. 61.

    Los GV, Encell LP, McDougall MG, Hartzell DD, Karassina N et al. 2008. HaloTag: a novel protein labeling technology for cell imaging and protein analysis. ACS Chem. Biol. 3:373–82
    [Google Scholar]
62. 62.

    Keppler A, Gendreizig S, Gronemeyer T, Pick H, Vogel H, Johnsson K. 2003. A general method for the covalent labeling of fusion proteins with small molecules in vivo. Nat. Biotechnol. 21:86–89
    [Google Scholar]
63. 63.

    Gautier A, Juillerat A, Heinis C, Corrêa IR Jr., Kindermann M et al. 2008. An engineered protein tag for multiprotein labeling in living cells. Chem. Biol. 15:128–36
    [Google Scholar]
64. 64.

    Kompa J, Bruins J, Glogger M, Wilhelm J, Frei MS et al. 2023. Exchangeable HaloTag ligands for super-resolution fluorescence microscopy. J. Am. Chem. Soc. 145:53075–83
    [Google Scholar]
65. 65.

    Lukinavicius G, Umezawa K, Olivier N, Honigmann A, Yang GY et al. 2013. A near-infrared fluorophore for live-cell super-resolution microscopy of cellular proteins. Nat. Chem. 5:132–39
    [Google Scholar]
66. 66.

    Grimm JB, English BP, Chen J, Slaughter JP, Zhang Z et al. 2015. A general method to improve fluorophores for live-cell and single-molecule microscopy. Nat. Methods 12:244–50
    [Google Scholar]
67. 67.

    Liu Z, Legant WR, Chen B-C, Li L, Grimm JB et al. 2014. 3D imaging of Sox2 enhancer clusters in embryonic stem cells. eLife 3:e04236
    [Google Scholar]
68. 68.

    Knight SC, Xie LQ, Deng WL, Guglielmi B, Witkowsky LB et al. 2015. Dynamics of CRISPR-Cas9 genome interrogation in living cells. Science 350:823–26
    [Google Scholar]
69. 69.

    Yanagawa M, Hiroshima M, Togashi Y, Abe M, Yamashita T et al. 2018. Single-molecule diffusion-based estimation of ligand effects on G protein–coupled receptors. Sci. Signal. 11:eaao1917
    [Google Scholar]
70. 70.

    Weiss S. 1999. Fluorescence spectroscopy of single biomolecules. Science 283:1676–83
    [Google Scholar]
71. 71.

    Wang Q, Moerner WE. 2014. Single-molecule motions enable direct visualization of biomolecular interactions in solution. Nat. Methods 11:555–58
    [Google Scholar]
72. 72.

    Chen Y-I, Sripati MP, Nguyen TD, Chang Y-J, Kuo Y-A et al. 2021. Recent developments in the characterization of nucleic acid hybridization kinetics. Curr. Opin. Biomed. Eng. 19:100305
    [Google Scholar]
73. 73.

    Deniz AA, Dahan M, Grunwell JR, Ha T, Faulhaber AE et al. 1999. Single-pair fluorescence resonance energy transfer on freely diffusing molecules: observation of Förster distance dependence and subpopulations. PNAS 96:3670–75
    [Google Scholar]
74. 74.

    Kapanidis AN, Lee NK, Laurence TA, Doose S, Margeat E, Weiss S. 2004. Fluorescence-aided molecule sorting: analysis of structure and interactions by alternating-laser excitation of single molecules. PNAS 101:8936–41
    [Google Scholar]
75. 75.

    Lipman EA, Schuler B, Bakajin O, Eaton WA. 2003. Single-molecule measurement of protein folding kinetics. Science 301:1233–35
    [Google Scholar]
76. 76.

    Zhang CY, Yeh HC, Kuroki MT, Wang TH. 2005. Single-quantum-dot-based DNA nanosensor. Nat. Mater. 4:826–31
    [Google Scholar]
77. 77.

    Yeh HC, Ho YP, Shih IM, Wang TH. 2006. Homogeneous point mutation detection by quantum dot-mediated two-color fluorescence coincidence analysis. Nucleic Acids Res 34:e35
    [Google Scholar]
78. 78.

    Johnson-Buck A, Su X, Giraldez MD, Zhao M, Tewari M, Walter NG. 2015. Kinetic fingerprinting to identify and count single nucleic acids. Nat. Biotechnol. 33:730–32
    [Google Scholar]
79. 79.

    Sambongi Y, Iko Y, Tanabe M, Omote H, Iwamoto-Kihara A et al. 1999. Mechanical rotation of the c subunit oligomer in ATP synthase (F0F1): direct observation. Science 286:1722–24
    [Google Scholar]
80. 80.

    Tokunaga M, Imamoto N, Sakata-Sogawa K. 2008. Highly inclined thin illumination enables clear single-molecule imaging in cells. Nat. Methods 5:159–61
    [Google Scholar]
81. 81.

    Izeddin I, Récamier V, Bosanac L, Cissé II, Boudarene L et al. 2014. Single-molecule tracking in live cells reveals distinct target-search strategies of transcription factors in the nucleus. eLife 3:e02230
    [Google Scholar]
82. 82.

    Hu YS, Zimmerley M, Li Y, Watters R, Cang H. 2014. Single-molecule super-resolution light-sheet microscopy. ChemPhysChem 15:577–86
    [Google Scholar]
83. 83.

    Huisken J, Swoger J, Del Bene F, Wittbrodt J, Stelzer EH. 2004. Optical sectioning deep inside live embryos by selective plane illumination microscopy. Science 305:1007–9
    [Google Scholar]
84. 84.

    Ritter JG, Veith R, Veenendaal A, Siebrasse JP, Kubitscheck U. 2010. Light sheet microscopy for single molecule tracking in living tissue. PLOS ONE 5:e11639
    [Google Scholar]
85. 85.

    Zanacchi FC, Lavagnino Z, Donnorso MP, Del Bue A, Furia L et al. 2011. Live-cell 3D super-resolution imaging in thick biological samples. Nat. Methods 8:1047–49
    [Google Scholar]
86. 86.

    Chen JJ, Zhang ZJ, Li L, Chen BC, Revyakin A et al. 2014. Single-molecule dynamics of enhanceosome assembly in embryonic stem cells. Cell 156:1274–85
    [Google Scholar]
87. 87.

    Funatsu T, Harada Y, Tokunaga M, Saito K, Yanagida T. 1995. Imaging of single fluorescent molecules and individual ATP turnovers by single myosin molecules in aqueous solution. Nature 374:555–59
    [Google Scholar]
88. 88.

    Tokunaga M, Kitamura K, Saito K, Iwane AH, Yanagida T. 1997. Single molecule imaging of fluorophores and enzymatic reactions achieved by objective-type total internal reflection fluorescence microscopy. Biochem. Biophys. Res. Commun. 235:47–53
    [Google Scholar]
89. 89.

    Keller PJ, Schmidt AD, Wittbrodt J, Stelzer EH. 2008. Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy. Science 322:1065–69
    [Google Scholar]
90. 90.

    Planchon TA, Gao L, Milkie DE, Davidson MW, Galbraith JA et al. 2011. Rapid three-dimensional isotropic imaging of living cells using Bessel beam plane illumination. Nat. Methods 8:417–23
    [Google Scholar]
91. 91.

    Chen BC, Legant WR, Wang K, Shao L, Milkie DE et al. 2014. Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution. Science 346:1257998
    [Google Scholar]
92. 92.

    Prabhat P, Ram S, Ward ES, Ober RJ. 2004. Simultaneous imaging of different focal planes in fluorescence microscopy for the study of cellular dynamics in three dimensions. IEEE Trans. Nanobiosci. 3:237–42
    [Google Scholar]
93. 93.

    Toprak E, Balci H, Blehm BH, Selvin PR. 2007. Three-dimensional particle tracking via bifocal imaging. Nano Lett 7:2043–45
    [Google Scholar]
94. 94.

    Juette MF, Gould TJ, Lessard MD, Mlodzianoski MJ, Nagpure BS et al. 2008. Three-dimensional sub-100 nm resolution fluorescence microscopy of thick samples. Nat. Methods 5:527–29
    [Google Scholar]
95. 95.

    Abrahamsson S, Chen JJ, Hajj B, Stallinga S, Katsov AY et al. 2013. Fast multicolor 3D imaging using aberration-corrected multifocus microscopy. Nat. Methods 10:60–63
    [Google Scholar]
96. 96.

    Shtengel G, Galbraith JA, Galbraith CG, Lippincott-Schwartz J, Gillette JM et al. 2009. Interferometric fluorescent super-resolution microscopy resolves 3D cellular ultrastructure. PNAS 106:3125–30
    [Google Scholar]
97. 97.

    Aquino D, Schönle A, Geisler C, Middendorff CV, Wurm CA et al. 2011. Two-color nanoscopy of three-dimensional volumes by 4Pi detection of stochastically switched fluorophores. Nat. Methods 8:353–59
    [Google Scholar]
98. 98.

    Ram S, Kim D, Ober RJ, Ward ES. 2012. 3D single molecule tracking with multifocal plane microscopy reveals rapid intercellular transferrin transport at epithelial cell barriers. Biophys. J. 103:1594–603
    [Google Scholar]
99. 99.

    Tahmasbi A, Ram S, Chao J, Abraham AV, Tang FW et al. 2014. Designing the focal plane spacing for multifocal plane microscopy. Opt. Express 22:16706–21
    [Google Scholar]
100. 100.

     Hajj B, Wisniewski J, El Beheiry M, Chen JJ, Revyakin A et al. 2014. Whole-cell, multicolor superresolution imaging using volumetric multifocus microscopy. PNAS 111:17480–85
     [Google Scholar]
101. 101.

     Smith CS, Preibisch S, Joseph A, Abrahamsson S, Rieger B et al. 2015. Nuclear accessibility of β-actin mRNA is measured by 3D single-molecule real-time tracking. J. Cell Biol. 209:609–19
     [Google Scholar]
102. 102.

     Kao HP, Verkman AS. 1994. Tracking of single fluorescent particles in three dimensions: use of cylindrical optics to encode particle position. Biophys. J. 67:1291–300
     [Google Scholar]
103. 103.

     Izeddin I, El Beheiry M, Andilla J, Ciepielewski D, Darzacq X, Dahan M 2012. PSF shaping using adaptive optics for three-dimensional single-molecule super-resolution imaging and tracking. Opt. Express 20:4957–67
     [Google Scholar]
104. 104.

     Pavani SRP, Piestun R. 2008. High-efficiency rotating point spread functions. Opt. Express 16:3484–89
     [Google Scholar]
105. 105.

     Huang B, Wang W, Bates M, Zhuang X. 2008. Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy. Science 319:810–13
     [Google Scholar]
106. 106.

     Jones SA, Shim S-H, He J, Zhuang X. 2011. Fast, three-dimensional super-resolution imaging of live cells. Nat. Methods 8:499–505
     [Google Scholar]
107. 107.

     Lien C-H, Lin C-Y, Chen S-J, Chien F-C. 2014. Dynamic particle tracking via temporal focusing multiphoton microscopy with astigmatism imaging. Opt. Express 22:27290–99
     [Google Scholar]
108. 108.

     Li Y, Hu Y, Cang H. 2013. Light sheet microscopy for tracking single molecules on the apical surface of living cells. J. Phys. Chem. B 117:15503–11
     [Google Scholar]
109. 109.

     Spille J-H, Kaminski TP, Scherer K, Rinne JS, Heckel A, Kubitscheck U. 2015. Direct observation of mobility state transitions in RNA trajectories by sensitive single molecule feedback tracking. Nucleic Acids Res 43:e14
     [Google Scholar]
110. 110.

     Thompson MA, Lew MD, Badieirostami M, Moerner WE. 2010. Localizing and tracking single nanoscale emitters in three dimensions with high spatiotemporal resolution using a double-helix point spread function. Nano Lett 10:211–18
     [Google Scholar]
111. 111.

     Thompson MA, Casolari JM, Badieirostami M, Brown PO, Moerner WE. 2010. Three-dimensional tracking of single mRNA particles in Saccharomyces cerevisiae using a double-helix point spread function. PNAS 107:17864–71
     [Google Scholar]
112. 112.

     Badieirostami M, Lew MD, Thompson MA, Moerner W. 2010. Three-dimensional localization precision of the double-helix point spread function versus astigmatism and biplane. Appl. Phys. Lett. 97:161103
     [Google Scholar]
113. 113.

     Shechtman Y, Weiss LE, Backer AS, Sahl SJ, Moerner W. 2015. Precise three-dimensional scan-free multiple-particle tracking over large axial ranges with tetrapod point spread functions. Nano Lett 15:4194–99
     [Google Scholar]
114. 114.

     Jia S, Vaughan JC, Zhuang X. 2014. Isotropic three-dimensional super-resolution imaging with a self-bending point spread function. Nat. Photon. 8:302–6
     [Google Scholar]
115. 115.

     Lew MD, Lee SF, Badieirostami M, Moerner W. 2011. Corkscrew point spread function for far-field three-dimensional nanoscale localization of pointlike objects. Opt. Lett. 36:202–4
     [Google Scholar]
116. 116.

     Backer AS, Backlund MP, von Diezmann AR, Sahl SJ, Moerner W. 2014. A bisected pupil for studying single-molecule orientational dynamics and its application to three-dimensional super-resolution microscopy. Appl. Phys. Lett. 104:193701
     [Google Scholar]
117. 117.

     Gustavsson AK, Petrov PN, Lee MY, Shechtman Y, Moerner WE. 2018. 3D single-molecule super-resolution microscopy with a tilted light sheet. Nat. Commun. 9:123
     [Google Scholar]
118. 118.

     Gustavsson A-K, Ghosh RP, Petrov PN, Liphardt JT, Moerner W. 2022. Fast and parallel nanoscale three-dimensional tracking of heterogeneous mammalian chromatin dynamics. Mol. Biol. Cell 33:ar47
     [Google Scholar]
119. 119.

     Kanchanawong P, Shtengel G, Pasapera AM, Ramko EB, Davidson MW et al. 2010. Nanoscale architecture of integrin-based cell adhesions. Nature 468:580–84
     [Google Scholar]
120. 120.

     Xia S, Lim YB, Zhang Z, Wang Y, Zhang S et al. 2019. Nanoscale architecture of the cortical actin cytoskeleton in embryonic stem cells. Cell Rep 28:1251–67.e7
     [Google Scholar]
121. 121.

     Wells NP, Lessard GA, Werner JH. 2008. Confocal, three-dimensional tracking of individual quantum dots in high-background environments. Anal. Chem. 80:9830–34
     [Google Scholar]
122. 122.

     Wells NP, Lessard GA, Goodwin PM, Phipps ME, Cutler PJ et al. 2010. Time-resolved three-dimensional molecular tracking in live cells. Nano Lett 10:4732–37
     [Google Scholar]
123. 123.

     DeVore M, Stich D, Keller A, Cleyrat C, Phipps M et al. 2015. Note: Time-gated 3D single quantum dot tracking with simultaneous spinning disk imaging. Rev. Sci. Instrum. 86:126102
     [Google Scholar]
124. 124.

     Berg HC. 1971. How to track bacteria. Rev. Sci. Instrum. 42:868–71
     [Google Scholar]
125. 125.

     Cang H, Xu CS, Montiel D, Yang H. 2007. Guiding a confocal microscope by single fluorescent nanoparticles. Opt. Lett. 32:2729–31
     [Google Scholar]
126. 126.

     Xu CS, Cang H, Montiel D, Yang H. 2007. Rapid and quantitative sizing of nanoparticles using three-dimensional single-particle tracking. J. Phys. Chem. C 111:32–35
     [Google Scholar]
127. 127.

     Lessard GA, Goodwin PM, Werner JH. 2007. Three-dimensional tracking of individual quantum dots. Appl. Phys. Lett. 91:224106
     [Google Scholar]
128. 128.

     DeVore MS, Stich DG, Keller AM, Ghosh Y, Goodwin PM et al. 2015. Three dimensional time-gated tracking of non-blinking quantum dots in live cells. Proc. SPIE 9338, Int. Soc. Optics Photon. 933812: https://doi.org/10.1117/12.2082943
     [Google Scholar]
129. 129.

     Berglund A, Mabuchi H. 2005. Tracking-FCS: fluorescence correlation spectroscopy of individual particles. Opt. Express 13:8069–82
     [Google Scholar]
130. 130.

     McHale K, Berglund AJ, Mabuchi H. 2007. Quantum dot photon statistics measured by three-dimensional particle tracking. Nano Lett 7:3535–39
     [Google Scholar]
131. 131.

     Katayama Y, Burkacky O, Meyer M, Bräuchle C, Gratton E, Lamb DC. 2009. Real-time nanomicroscopy via three-dimensional single-particle tracking. ChemPhysChem 10:2458–64
     [Google Scholar]
132. 132.

     Du K, Liddle JA, Berglund AJ. 2012. Three-dimensional real-time tracking of nanoparticles at an oil–water interface. Langmuir 28:9181–88
     [Google Scholar]
133. 133.

     Du K, Ko SH, Gallatin GM, Yoon HP, Liddle JA, Berglund AJ 2013. Quantum dot-DNA origami binding: a single particle, 3D, real-time tracking study. Chem. Commun. 49:907–9
     [Google Scholar]
134. 134.

     Wang Q, Moerner WE. 2010. Optimal strategy for trapping single fluorescent molecules in solution using the ABEL trap. Appl. Phys. B 99:23–30
     [Google Scholar]
135. 135.

     Germann JA, Davis LM. 2014. Three-dimensional tracking of a single fluorescent nanoparticle using four-focus excitation in a confocal microscope. Opt. Express 22:5641–50
     [Google Scholar]
136. 136.

     Perillo E, Liu Y-L, Liu C, Yeh H-C, Dunn AK. 2015. Single particle tracking through highly scattering media with multiplexed two-photon excitation. Proc. SPIE 9331, Single Mol. Spectr. Superresolut. Imag. VIII, 933107. https://doi.org/10.1117/12.2079897
     [Google Scholar]
137. 137.

     Liu C, Liu Y-L, Perillo E, Jiang N, Dunn A, Yeh H-C. 2015. Improving z-tracking accuracy in the two-photon single-particle tracking microscope. Appl. Phys. Lett. 107:153701
     [Google Scholar]
138. 138.

     Sahl SJ, Leutenegger M, Hilbert M, Hell SW, Eggeling C. 2010. Fast molecular tracking maps nanoscale dynamics of plasma membrane lipids. PNAS 107:6829–34
     [Google Scholar]
139. 139.

     Sahl SJ, Leutenegger M, Hell SW, Eggeling C. 2014. High-resolution tracking of single-molecule diffusion in membranes by confocalized and spatially differentiated fluorescence photon stream recording. ChemPhysChem 15:771–83
     [Google Scholar]
140. 140.

     Gwosch KC, Pape JK, Balzarotti F, Hoess P, Ellenberg J et al. 2020. MINFLUX nanoscopy delivers 3D multicolor nanometer resolution in cells. Nat. Methods 17:217–24
     [Google Scholar]
141. 141.

     Pape JK, Stephan T, Balzarotti F, Büchner R, Lange F et al. 2020. Multicolor 3D MINFLUX nanoscopy of mitochondrial MICOS proteins. PNAS 117:20607–14
     [Google Scholar]
142. 142.

     Balzarotti F, Eilers Y, Gwosch KC, Gynnå AH, Westphal V et al. 2017. Nanometer resolution imaging and tracking of fluorescent molecules with minimal photon fluxes. Science 355:606–12
     [Google Scholar]
143. 143.

     Masullo LA, Steiner F, Zähringer J, Lopez LF, Bohlen J et al. 2021. Pulsed interleaved minflux. Nano Lett 21:840–46
     [Google Scholar]
144. 144.

     Pertsinidis A, Zhang Y, Chu S. 2010. Subnanometre single-molecule localization, registration and distance measurements. Nature 466:647–51
     [Google Scholar]
145. 145.

     Manzo C, Garcia-Parajo MF. 2015. A review of progress in single particle tracking: from methods to biophysical insights. Rep. Progress Phys. 78:124601
     [Google Scholar]
146. 146.

     Saxton MJ. 2008. Single-particle tracking: connecting the dots. Nat. Methods 5:671–72
     [Google Scholar]
147. 147.

     Jaqaman K, Loerke D, Mettlen M, Kuwata H, Grinstein S et al. 2008. Robust single-particle tracking in live-cell time-lapse sequences. Nat. Methods 5:695–702
     [Google Scholar]
148. 148.

     Chenouard N, Smal I, de Chaumont F, Maška M, Sbalzarini IF et al. 2014. Objective comparison of particle tracking methods. Nat. Methods 11:281–89
     [Google Scholar]
149. 149.

     Das R, Cairo CW, Coombs D. 2009. A hidden Markov model for single particle tracks quantifies dynamic interactions between LFA-1 and the actin cytoskeleton. PLOS Comput. Biol. 5:e1000556
     [Google Scholar]
150. 150.

     Persson F, Lindén M, Unoson C, Elf J. 2013. Extracting intracellular diffusive states and transition rates from single-molecule tracking data. Nat. Methods 10:265–69
     [Google Scholar]
151. 151.

     Robson A, Burrage K, Leake MC. 2013. Inferring diffusion in single live cells at the single-molecule level. Philos. Trans. R. Soc. B 368:20120029
     [Google Scholar]
152. 152.

     Masson J-B, Dionne P, Salvatico C, Renner M, Specht CG et al. 2014. Mapping the energy and diffusion landscapes of membrane proteins at the cell surface using high-density single-molecule imaging and Bayesian inference: application to the multiscale dynamics of glycine receptors in the neuronal membrane. Biophys. J. 106:74–83
     [Google Scholar]
153. 153.

     Helmuth JA, Burckhardt CJ, Koumoutsakos P, Greber UF, Sbalzarini IF. 2007. A novel supervised trajectory segmentation algorithm identifies distinct types of human adenovirus motion in host cells. J. Struct. Biol. 159:347–58
     [Google Scholar]
154. 154.

     Wagner T, Kroll A, Haramagatti CR, Lipinski H-G, Wiemann M. 2017. Classification and segmentation of nanoparticle diffusion trajectories in cellular micro environments. PLOS ONE 12:e0170165
     [Google Scholar]
155. 155.

     Dosset P, Rassam P, Fernandez L, Espenel C, Rubinstein E et al. 2016. Automatic detection of diffusion modes within biological membranes using back-propagation neural network. BMC Bioinform. 17:197
     [Google Scholar]
156. 156.

     Qian H, Sheetz MP, Elson EL. 1991. Single particle tracking. Analysis of diffusion and flow in two-dimensional systems. Biophys. J. 60:910–21
     [Google Scholar]
157. 157.

     Michalet X. 2010. Mean square displacement analysis of single-particle trajectories with localization error: Brownian motion in an isotropic medium. Phys. Rev. E 82:041914
     [Google Scholar]
158. 158.

     Burov S, Tabei SA, Huynh T, Murrell MP, Philipson LH et al. 2013. Distribution of directional change as a signature of complex dynamics. PNAS 110:19689–94
     [Google Scholar]
159. 159.

     Miné-Hattab J, Heltberg M, Villemeur M, Guedj C, Mora T et al. 2021. Single molecule microscopy reveals key physical features of repair foci in living cells. eLife 10:e60577
     [Google Scholar]
160. 160.

     Cairo CW, Mirchev R, Golan DE. 2006. Cytoskeletal regulation couples LFA-1 conformational changes to receptor lateral mobility and clustering. Immunity 25:297–308
     [Google Scholar]
161. 161.

     Eddy SR. 1996. Hidden Markov models. Curr. Opin. Struct. Biol. 6:361–65
     [Google Scholar]
162. 162.

     Eddy SR. 2004. What is a hidden Markov model?. Nat. Biotechnol. 22:1315–16
     [Google Scholar]
163. 163.

     Slator PJ, Burroughs NJ. 2018. A hidden Markov model for detecting confinement in single-particle tracking trajectories. Biophys. J. 115:1741–54
     [Google Scholar]
164. 164.

     Elf J, Barkefors I. 2019. Single-molecule kinetics in living cells. Annu. Rev. Biochem. 88:635–59
     [Google Scholar]
165. 165.

     Monnier N, Barry Z, Park HY, Su K-C, Katz Z et al. 2015. Inferring transient particle transport dynamics in live cells. Nat. Methods 12:838–40
     [Google Scholar]
166. 166.

     van de Schoot R, Depaoli S, King R, Kramer B, Märtens K et al. 2021. Bayesian statistics and modelling. Nat. Rev. Methods Primers 1:1
     [Google Scholar]
167. 167.

     Kowalek P, Loch-Olszewska H, Szwabiński J. 2019. Classification of diffusion modes in single-particle tracking data: feature-based versus deep-learning approach. Phys. Rev. E 100:032410
     [Google Scholar]
168. 168.

     Hadzic MCAS, Börner R, König SLB, Kowerko D, Sigel RKO. 2018. Reliable state identification and state transition detection in fluorescence intensity-based single-molecule Förster resonance energy-transfer data. J. Phys. Chem. B 122:6134–47
     [Google Scholar]
169. 169.

     Taylor WA. 2000. Change-Point Analysis: A Powerful New Tool for Detecting Changes Deerfield, IL: Baxter Healthcare Corp.
170. 170.

     Shuang B, Cooper D, Taylor JN, Kisley L, Chen J et al. 2014. Fast step transition and state identification (STaSI) for discrete single-molecule data analysis. J. Phys. Chem. Lett. 5:3157–61
     [Google Scholar]
171. 171.

     McKinney SA, Joo C, Ha T. 2006. Analysis of single-molecule FRET trajectories using hidden Markov modeling. Biophys. J. 91:1941–51
     [Google Scholar]
172. 172.

     Bronson JE, Fei J, Hofman JM, Gonzalez RL, Wiggins CH. 2009. Learning rates and states from biophysical time series: a Bayesian approach to model selection and single-molecule FRET data. Biophys. J. 97:3196–205
     [Google Scholar]
173. 173.

     van de Meent J-W, Bronson JE, Wiggins CH, Gonzalez RL. 2014. Empirical Bayes methods enable advanced population-level analyses of single-molecule FRET experiments. Biophys. J. 106:1327–37
     [Google Scholar]
174. 174.

     Işbilir A, Serfling R, Möller J, Thomas R, De Faveri C et al. 2021. Determination of G-protein–coupled receptor oligomerization by molecular brightness analyses in single cells. Nat. Protoc. 16:1419–51
     [Google Scholar]
175. 175.

     Ripley BD. 1977. Modelling spatial patterns. J. R. Stat. Soc. B 39:172–92
     [Google Scholar]
176. 176.

     Owen DM, Rentero C, Rossy J, Magenau A, Williamson D et al. 2010. PALM imaging and cluster analysis of protein heterogeneity at the cell surface. J. Biophoton. 3:446–54
     [Google Scholar]
177. 177.

     Endesfelder U, Malkusch S, Flottmann B, Mondry J, Liguzinski P et al. 2011. Chemically induced photoswitching of fluorescent probes—a general concept for super-resolution microscopy. Molecules 16:3106–18
     [Google Scholar]
178. 178.

     Besag J. 1977. Contribution to the discussion on Dr Ripley's paper. J. R. Stat. Soc. B 39:193–95
     [Google Scholar]
179. 179.

     Kiskowski MA, Hancock JF, Kenworthy AK. 2009. On the use of Ripley's K-function and its derivatives to analyze domain size. Biophys. J. 97:1095–103
     [Google Scholar]
180. 180.

     Martens KJA, Turkowyd B, Endesfelder U. 2022. Raw data to results: a hands-on introduction and overview of computational analysis for single-molecule localization microscopy. Front. Bioinform. 1:817254
     [Google Scholar]
181. 181.

     Ester M, Kriegel H-P, Sander J, Xu X. 1996. A density-based algorithm for discovering clusters in large spatial databases with noise. Proceedings of 2nd International Conference on Knowledge Discovery and Data Mining (KDD-96)226–31. New York: Assoc. Comput. Mach.
     [Google Scholar]
182. 182.

     Griffié J, Shannon M, Bromley CL, Boelen L, Burn GL et al. 2016. A Bayesian cluster analysis method for single-molecule localization microscopy data. Nat. Protocols 11:2499–514
     [Google Scholar]
183. 183.

     Nino DF, Djayakarsana D, Milstein JN. 2020. FOCAL3D: a 3-dimensional clustering package for single-molecule localization microscopy. PLOS Comput. Biol. 16:e1008479
     [Google Scholar]
184. 184.

     Levet F, Hosy E, Kechkar A, Butler C, Beghin A et al. 2015. SR-Tesseler: a method to segment and quantify localization-based super-resolution microscopy data. Nat. Methods 12:1065–71
     [Google Scholar]
185. 185.

     Andronov L, Orlov I, Lutz Y, Vonesch JL, Klaholz BP. 2016. ClusterViSu, a method for clustering of protein complexes by Voronoi tessellation in super-resolution microscopy. Sci. Rep. 6:24084
     [Google Scholar]
186. 186.

     Rubin-Delanchy P, Burn GL, Griffié J, Williamson DJ, Heard NA et al. 2015. Bayesian cluster identification in single-molecule localization microscopy data. Nat. Methods 12:1072–76
     [Google Scholar]
187. 187.

     Ha T, Tinnefeld P. 2012. Photophysics of fluorescence probes for single molecule biophysics and super-resolution imaging. Annu. Rev. Phys. Chem. 63:595–617
     [Google Scholar]
188. 188.

     Peng CS, Zhang Y, Liu Q, Marti GE, Huang Y-WA et al. 2022. Nanometer-resolution long-term tracking of single cargos reveals dynein motor mechanisms. bioRxiv 475120. https://doi.org/10.1101/2022.01.05.475120
     [Crossref]
189. 189.

     Kumarasinghe R, Higgins ED, Ito T, Higgins DA. 2016. Spectroscopic and polarization-dependent single-molecule tracking reveal the one-dimensional diffusion pathways in surfactant-templated mesoporous silica. J. Phys. Chem. C 120:715–23
     [Google Scholar]
190. 190.

     Cutler PJ, Malik MD, Liu S, Byars JM, Lidke DS, Lidke KA. 2013. Multi-color quantum dot tracking using a high-speed hyperspectral line-scanning microscope. PLOS ONE 8:e64320
     [Google Scholar]
191. 191.

     Scipioni L, Rossetta A, Tedeschi G, Gratton E. 2021. Phasor S-FLIM: a new paradigm for fast and robust spectral fluorescence lifetime imaging. Nat. Methods 18:542–50
     [Google Scholar]
192. 192.

     Goda K, Tsia K, Jalali B. 2009. Serial time-encoded amplified imaging for real-time observation of fast dynamic phenomena. Nature 458:1145–49
     [Google Scholar]
193. 193.

     Wu J, Liang Y, Chen S, Hsu C-L, Chavarha M et al. 2020. Kilohertz two-photon fluorescence microscopy imaging of neural activity in vivo. Nat. Methods 17:287–90
     [Google Scholar]
194. 194.

     Karpf S, Riche CT, Di Carlo D, Goel A, Zeiger WA et al. 2020. Spectro-temporal encoded multiphoton microscopy and fluorescence lifetime imaging at kilohertz frame-rates. Nat. Commun. 11:2062
     [Google Scholar]
195. 195.

     Lessard GA, Goodwin PM, Werner JH. 2006. Three-dimensional tracking of fluorescent particles. Proc. SPIE 6092 Ultrasens. Single-Mol. Detect. Technol. 60925. https://doi.org/10.1117/12.650191
     [Google Scholar]
196. 196.

     Juette MF, Bewersdorf J. 2010. Three-dimensional tracking of single fluorescent particles with submillisecond temporal resolution. Nano Lett 10:4657–63
     [Google Scholar]
197. 197.

     Levi V, Ruan QQ, Gratton E. 2005. 3-D particle tracking in a two-photon microscope: Application to the study of molecular dynamics in cells. Biophys. J. 88:2919–28
     [Google Scholar]
198. 198.

     Levi V, Ruan Q, Kis-Petikova K, Gratton E. 2003. Scanning FCS, a novel method for three-dimensional particle tracking. Biochem. Soc. Trans. 31:997–1000
     [Google Scholar]
199. 199.

     Annibale P, Dvornikov A, Gratton E. 2015. Electrically tunable lens speeds up 3D orbital tracking. Biomed. Opt. Express 6:2181–91
     [Google Scholar]
200. 200.

     Lanzanò L, Gratton E. 2014. Orbital single particle tracking on a commercial confocal microscope using piezoelectric stage feedback. Methods Appl. Fluoresc. 2:024010
     [Google Scholar]
201. 201.

     Hou S, Lang X, Welsher K. 2017. Robust real-time 3D single-particle tracking using a dynamically moving laser spot. Opt. Lett. 42:2390–93
     [Google Scholar]
202. 202.

     Hou S, Johnson C, Welsher K. 2019. Real-time 3D single particle tracking: towards live cell spectroscopy. Molecules 24:2826
     [Google Scholar]
203. 203.

     Hou S, Welsher K 2019. An adaptive real-time 3D single particle tracking method for monitoring viral first contacts. Small 15:1903039
     [Google Scholar]