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Annual Review of Biophysics

Volume 44, 2015

Single-Cell Physiology

Abstract

Single-cell techniques have a long history of unveiling fundamental paradigms in biology. Recent improvements in the throughput, resolution, and availability of microfluidics, computational power, and genetically encoded fluorescence have led to a modern renaissance in microbial physiology. This resurgence in research activity has offered new perspectives on physiological processes such as growth, cell cycle, and cell size of model organisms such as . We expect these single-cell techniques, coupled with the molecular revolution of biology's recent half-century, to continue illuminating unforeseen processes and patterns in microorganisms, the bedrock of biological science. In this article we review major open questions in single-cell physiology, provide a brief introduction to the techniques for scientists of diverse backgrounds, and highlight some pervasive issues and their solutions.

Keyword(s): cell cycle, growth, microbiology, microfluidics, quantitative biology, systems biology
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2015-06-22
2024-04-20
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Literature Cited

  1. Ackermann M, Stearns SC, Jenal U. 1.  2003. Senescence in a bacterium with asymmetric division. Science 300:1920 [Google Scholar]
  2. Adler M, Erickstad M, Gutierrez E, Groisman A. 2.  2012. Studies of bacterial aerotaxis in a microfluidic device. Lab Chip 12:4835–47 [Google Scholar]
  3. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. 3.  2003. Molecular Biology of the Cell New York: Garland Science
  4. Amir A, Babaeipour F, McIntosh DB, Nelson DR, Jun S. 4.  2014. Bending forces plastically deform growing bacterial cell walls. PNAS 111:5778–83 [Google Scholar]
  5. Andersen DC, Swartz J, Ryll T, Lin N, Snedecor B. 5.  2001. Metabolic oscillations in an E. coli fermentation. Biotechnol. Bioeng. 75:212–18 [Google Scholar]
  6. Arnoldini M, Vizcarra IA, Peña-Miller R, Stocker N, Diard M. 6.  et al. 2014. Bistable expression of virulence genes in Salmonella leads to the formation of an antibiotic-tolerant subpopulation. PLOS Biol. 12:e1001928 [Google Scholar]
  7. Ashkin A, Dziedzic J, Bjorkholm JE, Chu S. 7.  1986. Observation of a single-beam gradient-force optical trap for dielectric particles in air. Opt. Lett. 22:816–18 [Google Scholar]
  8. Ashkin A, Dziedzic J, Yamane T. 8.  1987. Optical trapping and manipulation of single cells using infrared laser beams. Nature 330:769–71 [Google Scholar]
  9. Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y. 9.  et al. 2006. Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol. Syst. Biol. 2:2006.0008 [Google Scholar]
  10. Balaban NQ, Merrin J, Chait R, Kowalik L, Leibler S. 10.  2004. Bacterial persistence as a phenotypic switch. Science 305:1622–25 [Google Scholar]
  11. Balagadde F, You L, Hansen C, Arnold F, Quake S. 11.  2005. Long-term monitoring of bacteria undergoing programmed population control in a microchemostat. Science 309:137–40 [Google Scholar]
  12. Barker CS, Prüss BM, Matsumura P. 12.  2004. Increased motility of Escherichia coli by insertion sequence element integration into the regulatory region of the flhD operon (MG1655). J. Bacteriol. 186:7529–37 [Google Scholar]
  13. Barondess J, Beckwith J. 13.  1995. bor gene of phage λ, involved in serum resistance, encodes a widely conserved outer membrane lipoprotein. J. Bacteriol. 177:1247–53 [Google Scholar]
  14. Bates D, Kleckner N. 14.  2005. Chromosome and replisome dynamics in E. coli: Loss of sister cohesion triggers global chromosome movement and mediates chromosome segregation. Cell 121:899–911 [Google Scholar]
  15. Bayne-Jones S, Adolph EF. 15.  1932. Growth in size of micro-organisms measured from motion pictures: II. Bacillus megatherium. J. Cell. Comp. Physiol. 1:388–407 [Google Scholar]
  16. Benson RC, Meyer RA, Zaruba ME, McKhann GM. 16.  1979. Cellular autofluorescence—Is it due to flavins?. J. Histochem. Cytochem. 27:44–48 [Google Scholar]
  17. Berg HC. 17.  2003. The rotary motor of bacterial flagella. Annu. Rev. Biochem. 72:9–54 [Google Scholar]
  18. Blair DF, Berg HC. 18.  1990. The MotA protein of E. coli is a proton-conducting component of the flagellar motor. Cell 60:439–49 [Google Scholar]
  19. Blattner FR, Plunkett GI, Bloch CA, Perna NT, Burland V. 19.  et al. 1997. The complete genome sequence of Escherichia coli K-12. Science 277:1453–62 [Google Scholar]
  20. Block SM. 20.  1998. Construction of optical tweezers. Cells: A Laboratory Manual 3 D Spector, R Goldman, L Leinwand 81.1–81.14 Cold Spring Harbor, NY: Cold Spring Harbor Press [Google Scholar]
  21. Brinkkötter A, Klöss H, Alpert CA, Lengeler JW. 21.  2000. Pathways for the utilization of N-acetyl-galactosamine and galactosamine in Escherichia coli. Mol. Microbiol. 37:125–35 [Google Scholar]
  22. Campbell A. 22.  1957. Synchronization of cell division. Bacteriol. Rev. 21:263–72 [Google Scholar]
  23. Campos M, Surovtsev IV, Kato S, Paintdakhi A, Beltran B. 23.  et al. 2014. A constant size extension drives bacterial cell size homeostasis. Cell 159:1433–466 [Google Scholar]
  24. Carpenter AE, Jones TR, Lamprecht MR, Clarke C, Kang IH. 24.  et al. 2006. CellProfiler: image analysis software for identifying and quantifying cell phenotypes. Genome Biol. 7:R100 [Google Scholar]
  25. Chance B, Cohen P, Jobsis F, Schoener B. 25.  1962. Intracellular oxidation-reduction states in vivo. Science 137:499–508 [Google Scholar]
  26. Cooper S. 26.  1969. Cell division and DNA replication following a shift to a richer medium. J. Mol. Biol. 43:1–11Shows that chromosome replication initiates once accumulation of hypothetical initiator(s) reaches a threshold; rate of accumulation depends on growth rate. [Google Scholar]
  27. Cooper S. 27.  2006. Regulation of DNA synthesis in bacteria: analysis of the Bates/Kleckner licensing/initiation-mass model for cell cycle control. Mol. Microbiol. 62:303–7 [Google Scholar]
  28. Cooper S, Helmstetter CE. 28.  1968. Chromosome replication and the division cycle of Escherichia coli B/r. J. Mol. Biol. 31:3519–40Demonstrates that periods of chromosome replication and the gap between termination of replication and cell division are constant, independent of growth rate. [Google Scholar]
  29. DeLisa M, Valdes J, Bentley W. 29.  2001. Mapping stress-induced changes in autoinducer AI-2 production in chemostat-cultivated Escherichia coli K-12. J. Bacteriol. 183:2918–28 [Google Scholar]
  30. Dobell C. 30.  1923. Antony Van Leeuwenhoek and His “Little Animals” New York: Harcourt, Brace [Google Scholar]
  31. Domínguez-Escobar J, Chastanet A, Crevenna AH, Fromion V, Wedlich-Söldner R, Carballido-López R. 31.  2011. Processive movement of MreB-associated cell wall biosynthetic complexes in bacteria. Science 333:225–28 [Google Scholar]
  32. Donachie W. 32.  1968. Relationship between cell size and time of initiation of DNA replication. Nature 219:1077–79Introduces notion of critical mass at initiation of chromosome replication: Cells initiate replication at a constant cell mass per origin of replication. [Google Scholar]
  33. Donnert G, Eggeling C, Hell SW. 33.  2009. Triplet-relaxation microscopy with bunched pulsed excitation. Photochem. Photobiol. Sci. 8:481–85 [Google Scholar]
  34. Elowitz M, Levine A, Siggia E, Swain P. 34.  2002. Stochastic gene expression in a single cell. Science 297:1183–86Categorizes sources of noise in genetic networks as intrinsic and extrinsic noise. [Google Scholar]
  35. Freddolino PL, Amini S, Tavazoie S. 35.  2012. Newly identified genetic variations in common Escherichia coli MG1655 stock cultures. J. Bacteriol. 194:303–6 [Google Scholar]
  36. Frumkin D, Wasserstrom A, Itzkovitz S, Stern T, Harmelin A. 36.  et al. 2008. Cell lineage analysis of a mouse tumor. Cancer Res. 68:5924–31 [Google Scholar]
  37. Garner EC, Bernard R, Wang W, Zhuang X, Rudner DZ, Mitchison T. 37.  2011. Coupled, circumferential motions of the cell wall synthesis machinery and MreB filaments in B. subtilis. Science 333:222–25 [Google Scholar]
  38. Godin M, Delgado FF, Son S, Grover WH, Bryan AK. 38.  et al. 2010. Using buoyant mass to measure the growth of single cells. Nat. Methods 7:387–90Uses buoyant mass to measure the relationship between cell mass and mass increase rate. [Google Scholar]
  39. Greenbaum L, Rothmann C, Lavie R, Malik Z. 39.  2000. Green fluorescent protein photobleaching: a model for protein damage by endogenous and exogenous singlet oxygen. Biol. Chem. 381:1251–58 [Google Scholar]
  40. Groisman A, Lobo C, Cho H. 40.  2005. A microfluidic chemostat for experiments with bacterial and yeast cells. Nat. Methods 2:685–89 [Google Scholar]
  41. Guo MT, Rotem A, Heyman JA, Weitz DA. 41.  2012. Droplet microfluidics for high-throughput biological assays. Lab Chip 12:2146–55 [Google Scholar]
  42. Harvey R, Marr A, Painter P. 42.  1967. Kinetics of growth of individual cells of Escherichia coli and Azotobacter agilis. J. Bacteriol. 93:605–17 [Google Scholar]
  43. Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K. 43.  et al. 2006. Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol. Syst. Biol. 2:2006.0007 [Google Scholar]
  44. Helmstetter C. 44.  1967. Rates of DNA synthesis during the division cycle of Escherichia coli B/r. J. Mol. Biol. 24:417–27 [Google Scholar]
  45. Helmstetter CE, Cummings DJ. 45.  1963. Bacterial synchronization by selection of cells at division. PNAS 50:767–74 [Google Scholar]
  46. Hill NS, Buske PJ, Shi Y, Levin PA. 46.  2013. A moonlighting enzyme links Escherichia coli cell size with central metabolism. PLOS Genet. 9:e1003663 [Google Scholar]
  47. Hoebe RA, Van Oven CH, Gadella TWJ, Dhonukshe PB, Van Noorden CJF, Manders EMM. 47.  2007. Controlled light-exposure microscopy reduces photobleaching and phototoxicity in fluorescence live-cell imaging. Nat. Biotechnol. 25:249–53 [Google Scholar]
  48. Hribar KC, Soman P, Warner J, Chung P, Chen S. 48.  2014. Light-assisted direct-write of 3D functional biomaterials. Lab Chip 14:268–75 [Google Scholar]
  49. Jacob F, Monod J. 49.  1961. Genetic regulatory mechanisms in the synthesis of proteins. J. Mol. Biol 3:3318–56 [Google Scholar]
  50. Jensen KF. 50.  1993. The Escherichia coli K-12 “wild types” W3110 and MG1655 have an rph frameshift mutation that leads to pyrimidine starvation due to low pyrE expression levels. J. Bacteriol. 175:3401–7 [Google Scholar]
  51. Johnson ID. 51.  2006. Practical considerations in the selection and application of fluorescent probes. Handbook of Biological Confocal Microscopy JB Pawley 353–67 New York: Springer [Google Scholar]
  52. Johnston GC, Ehrhardt CW, Lorincz A, Carter BLA. 52.  1979. Regulation of cell size in the yeast Saccharomyces cerevisiae. J. Bacteriol. 137:1–5 [Google Scholar]
  53. Jun S, Taheri-Araghi S. 53.  2014. Cell-size maintenance: universal strategy revealed. Trends Microbiol 23:4–6 [Google Scholar]
  54. Kalisky T, Quake SR. 54.  2011. Single-cell genomics. Nat. Methods 8:311–14 [Google Scholar]
  55. Keymer JE, Galajda P, Muldoon C, Park S, Austin RH. 55.  2006. Bacterial metapopulations in nanofabricated landscapes. PNAS 103:17290–95 [Google Scholar]
  56. Kitson PJ, Rosnes MH, Sans V, Dragone V, Cronin L. 56.  2012. Configurable 3D-printed millifluidic and microfluidic ‘lab on a chip’ reactionware devices. Lab Chip 12:3267–71 [Google Scholar]
  57. Kiviet DJ, Nghe P, Walker N, Boulineau S, Sunderlikova V, Tans SJ. 57.  2014. Stochasticity of metabolism and growth at the single-cell level. Nature 514:376–79 [Google Scholar]
  58. Koch AL. 58.  2001. Bacterial Growth and Form New York: Springer
  59. Koch AL, Schaechter M. 59.  1962. A model for statistics of the cell division process. J. Gen. Microbiol. 29:435–54 [Google Scholar]
  60. Landgraf D, Okumus B, Chien P, Baker TA, Paulsson J. 60.  2012. Segregation of molecules at cell division reveals native protein localization. Nat. Methods 9:480–82Explicitly demonstrates potential confounding effects of fluorescent fusion proteins in physiologic investigations. [Google Scholar]
  61. Landry ZC, Giovanonni SJ, Quake SR, Blainey PC. 61.  2013. Optofluidic cell selection from complex microbial communities for single-genome analysis. Methods Enzymol. 531:61–69 [Google Scholar]
  62. Lankford C, Byers B. 62.  1973. Bacterial assimilation of iron. Crit. Rev. Microbiol. 2:273–331 [Google Scholar]
  63. Lee JH, Lee J. 63.  2010. Indole as an intercellular signal in microbial communities. FEMS Microbiol. Rev. 34:426–44 [Google Scholar]
  64. Leung K, Zahn H, Leaver T, Konwar KM, Hanson NW. 64.  et al. 2012. A programmable droplet-based microfluidic device applied to multiparameter analysis of single microbes and microbial communities. PNAS 109:7665–70 [Google Scholar]
  65. Lindner AB, Madden R, Demarez A, Stewart EJ, Taddei F. 65.  2008. Asymmetric segregation of protein aggregates is associated with cellular aging and rejuvenation. PNAS 105:3076–81 [Google Scholar]
  66. Macaulay IC, Voet T. 66.  2014. Single cell genomics: advances and future perspectives. PLOS Genet. 10:e1004126 [Google Scholar]
  67. Männik J, Driessen R, Galajda P, Keymer JE, Dekker C. 67.  2009. Bacterial growth and motility in sub-micron constrictions. PNAS 106:14861–66 [Google Scholar]
  68. Mashburn-Warren LM, Whiteley M. 68.  2006. Special delivery: vesicle trafficking in prokaryotes. Mol. Microbiol. 61:839–46 [Google Scholar]
  69. Mitchison JM. 69.  1971. The Biology of the Cell Cycle Cambridge, UK: Cambridge Univ. Press
  70. Moffitt JR, Lee JB, Cluzel P. 70.  2012. The single-cell chemostat: an agarose-based, microfluidic device for high-throughput, single-cell studies of bacteria and bacterial communities. Lab Chip 12:1487–94 [Google Scholar]
  71. Monod J. 71.  1949. The growth of bacterial cultures. Annu. Rev. Microbiol. 3:371–94 [Google Scholar]
  72. Mortimer R, Johnston J. 72.  1959. Life span of individual yeast cells. Nature 183:1751–52 [Google Scholar]
  73. Nanninga N, Woldringh C. 73.  1985. Molecular Cytology of Escherichia coli: Cell Growth, Genome Duplication, and Cell Division London: Academic
  74. Norman TM, Lord ND, Paulsson J, Losick R. 74.  2013. Memory and modularity in cell-fate decision making. Nature 503:481–86 [Google Scholar]
  75. Novick A, Weiner M. 75.  1957. Enzyme induction as an all-or-none phenomenon. PNAS 43:553–66 [Google Scholar]
  76. Ozbudak EM, Thattai M, Kurtser I, Grossman AD, van Oudenaarden A. 76.  2002. Regulation of noise in the expression of a single gene. Nat. Genet. 31:69–73Shows that protein copy number noise is a function of translation (stochastic ribosomal activity) as opposed to transcription (gene expression). [Google Scholar]
  77. Ozbudak EM, Thattai M, Lim HN, Shraiman BI. Oudenaarden A. 77. , Van 2004. Multistability in the lactose utilization network of Escherichia coli. Nature 427:737–40 [Google Scholar]
  78. Rolfe MD, Rice CJ, Lucchini S, Pin C, Thompson A. 78.  et al. 2012. Lag phase is a distinct growth phase. J. Bacteriol. 194:686–701 [Google Scholar]
  79. Schaechter M, Maaløe O, Kjeldgaard NO. 79.  1958. Dependency on medium and temperature of cell size and chemical composition during balanced growth of Salmonella typhimurium. J. Gen. Microbiol. 19:592–606Introduces growth law stating that cell size is exponentially related to growth rate. [Google Scholar]
  80. Schaller RR. 80.  1997. Moore's law: past, present, and future. IEEE Spectrosc. 6:52–59 [Google Scholar]
  81. Shaner NC, Patterson GH, Davidson MW. 81.  2007. Advances in fluorescent protein technology. J. Cell Sci. 120:4247–60 [Google Scholar]
  82. Shaner NC, Steinbach PA, Tsien RY. 82.  2005. A guide to choosing fluorescent proteins. Nat. Methods 2:905–9 [Google Scholar]
  83. Sliusarenko O, Heinritz J, Emonet T, Jacobs-Wagner C. 83.  2011. High-throughput, subpixel precision analysis of bacterial morphogenesis and intracellular spatio-temporal dynamics. Mol. Microbiol. 80:612–27 [Google Scholar]
  84. So P, Dong C. 84.  2000. Two-photon excitation fluorescence microscopy. Annu. Rev. Biomed. Eng. 2:399–429 [Google Scholar]
  85. Son S, Grover W, Burg T, Manalis S. 85.  2008. Suspended microchannel resonators for ultralow volume universal detection. Anal. Chem. 80:4757–60 [Google Scholar]
  86. Soupene E, van Heeswijk WC, Plumbridge J, Stewart V, Bertenthal D. 86.  et al. 2003. Physiological studies of Escherichia coli strain MG1655: growth defects and apparent cross-regulation of gene expression. Am. Soc. Microbiol. 185:5611–26 [Google Scholar]
  87. Spivey EC, Xhemalce B, Shear JB, Finkelstein IJ. 87.  2014. 3D-printed microfluidic microdissector for high-throughput studies of cellular aging. Anal. Chem. 86:7406–12 [Google Scholar]
  88. Squires T, Quake SR. 88.  2005. Microfluidics: fluid physics at the nanoliter scale. Rev. Modern Phys. 77:977–1026 [Google Scholar]
  89. Starka J. 89.  1974. Avant-propos (foreword). Ann. Microbiol. 125B:133–34 [Google Scholar]
  90. Stewart EJ, Madden R, Paul G, Taddei F. 90.  2005. Aging and death in an organism that reproduces by morphologically symmetric division. PLOS Biol. 3:e45 [Google Scholar]
  91. Strack RL, Hein B, Bhattacharyya D, Hell SW, Keenan RJ, Glick BS. 91.  2009. A rapidly maturing far-red derivative of DsRed-Express2 for whole-cell labeling. Biochemistry 48:8279–81 [Google Scholar]
  92. Taheri-Araghi S, Bradde S, Sauls JT, Hill NS, Levin PA. 92.  et al. 2015. Cell size control in bacteria. Curr. Biol. http://dx.doi.org/10.1016/j.cub.2014.12.009 Demonstrates that bacteria maintain size homeostasis by adding a constant size in each cell cycle.
  93. Takeuchi S, DiLuzio WR, Weibel DB, Whitesides GM. 93.  2005. Controlling the shape of filamentous cells of Escherichia coli. Nano Lett. 5:1819–23 [Google Scholar]
  94. Turner L, Zhang R, Darnton NC, Berg HC. 94.  2010. Visualization of flagella during bacterial swarming. J. Bacteriol. 192:3259–67 [Google Scholar]
  95. Unger MA, Chou H-P, Thorsen T, Scherer A, Quake SR. 95.  2000. Monolithic microfabricated valves and pumps by multilayer soft lithography. Science 288:113–16 [Google Scholar]
  96. Van Teeffelen S, Wang S, Furchtgott L, Huang KC, Wingreen NS. 96.  et al. 2011. The bacterial actin MreB rotates, and rotation depends on cell-wall assembly. PNAS 108:15822–27 [Google Scholar]
  97. Voorn WJ, Koppes LJ, Grover N. 97.  1993. Mathematics of cell division in Escherichia coli. Curr. Top. Mol. Genet.187–94
  98. Wang P, Robert L, Pelletier J, Dang WL, Taddei F. 98.  et al. 2010. Robust growth of Escherichia coli. Curr. Biol. 20:1099–103Overturned widespread belief that cell age and growth rate were inversely correlated by using microfluidic growth chambers instead of agarose pads. [Google Scholar]
  99. Wang S, Arellano-Santoyo H, Combs PA, Shaevitz JW. 99.  2010. Actin-like cytoskeleton filaments contribute to cell mechanics in bacteria. PNAS 107:9182–85 [Google Scholar]
  100. Wang X, Kim Y, Ma Q, Hong SH, Pokusaeva K. 100.  et al. 2010. Cryptic prophages help bacteria cope with adverse environments. Nat. Commun. 1:147 [Google Scholar]
  101. Weart RB, Lee AH, Chien AC, Haeusser DP, Hill NS, Levin PA. 101.  2007. A metabolic sensor governing cell size in bacteria. Cell 130:335–47 [Google Scholar]
  102. Whitesides GM. 102.  2006. The origins and the future of microfluidics. Nature 442:368–73 [Google Scholar]
  103. Winkler J, Seybert A, König L, Pruggnaller S, Haselmann U. 103.  et al. 2010. Quantitative and spatio-temporal features of protein aggregation in Escherichia coli and consequences on protein quality control and cellular ageing. EMBO J. 29:910–23 [Google Scholar]
  104. Woldringh C, Grover N, Rosenberger R, Zaritsky A. 104.  1980. Dimensional rearrangement of rod-shaped bacteria following nutritional shift-up. II. Experiments with Escherichia coli B/r. J. Theor. Biol. 86:441–54 [Google Scholar]
  105. Xia Y, Whitesides GM. 105.  1998. Soft lithography. Annu. Rev. Mater. Sci. 28:153–84 [Google Scholar]
  106. Zhang Q, Lambert G, Liao D, Kim H, Robin K. 106.  et al. 2011. Acceleration of emergence of bacterial antibiotic resistance in connected microenvironments. Science 333:1764–67 [Google Scholar]
  107. Zipfel WR, Williams RM, Webb WW. 107.  2003. Nonlinear magic: multiphoton microscopy in the biosciences. Nat. Biotechnol. 21:1369–77 [Google Scholar]
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Single-Cell Physiology
Annual Review of Biophysics 44, 123 (2015); https://doi.org/10.1146/annurev-biophys-060414-034236
/content/journals/10.1146/annurev-biophys-060414-034236
/content/journals/10.1146/annurev-biophys-060414-034236
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