Biological structures that generate function can arise from fluctuations and local interactions of proteins by self-organization. To understand how these patterns can emerge, measurements of protein mobility and activity need to be combined.
Signalling networks often include reaction cycles, which can dynamically maintain a limited number of activity states. Such discrete network states can define key aspects of contrasting cellular behaviours.
Reaction cycles, which occur around preformed cellular templates, such as chromatin in mitosis, can spatially constrain signals by reaction–diffusion and thereby guide the formation of structures during cellular morphogenesis.
Supramolecular structures, such as the mitotic spindle, emerge from a complex interplay between a limited set of preformed templates and de novo structure formation by self-organization.
Concepts that describe the organization of insect colonies, such as the self-organized growth of a structure based on information gathered from work-in-progress (stigmergy), can provide useful analogies to cellular organization.
To understand intracellular communication and cellular organization, a recursive feedback loop between microscopic imaging and modelling will give us deeper insight into how the collective behaviour of nanometre-sized molecules generates functional structures on the micrometre scale of cells.
Signal transduction is the transfer of information about the compositional state of the extracellular environment to the intracellular cytoplasm that elicits a morphological or genetic response. In more general terms, this can also be the communication of the state of supramolecular structures, such as the plasma membrane or chromatin, in the cell. This information is relayed through space by the cytoplasm and is mediated by transitions between the steady states of the cytoplasm's reaction networks. To uncover the principles that underlie the generation of spatiotemporal patterns of activity which guide cellular behaviour, functional imaging techniques that report on the activity of molecules must be combined with imaging techniques that report on the mobility of molecules.
Subscribe to Journal
Get full journal access for 1 year
only $8.25 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Nicolis, G. & Prigogine Ilya. Self-organization in Nonequilibrum Systems: From Dissipative Structures to Order Through Fluctuations (Wiley, New York, 1977).
Grasse, P. P. La reconstruction du nid et les coordinations inter-individuelles chez Bellicositermes natalensis et Cubitermes sp. La theorie de la stigmergie: Essai d'interpretation du comportement des termites constructeurs. Insectes Sociaux 6, 41–81 (1959) (in French).
Bruinsma, O. H. An Analysis of Building Behaviour of the Termite Macrotermes subhyalinus (Rambur). Thesis, Wageningen Univ. (1979).
Camazine, S. et al. Self-Organization in Biological Systems (eds Anderson, P. W., Epstein, J. M., Foley, D. K., Levin, S. A. & Nowak, M. A.) (Princeton Univeristy Press, Princeton, 2001). A detailed and insightful overview about general concepts for organization and pattern formation in macroscopic biological systems.
Bouzigues, C., Morel, M., Triller, A. & Dahan, M. Asymmetric redistribution of GABA receptors during GABA gradient sensing by nerve growth cones analysed by single quantum dot imaging. Proc. Natl Acad. Sci. USA 104, 11251–11256 (2007). An elegant study combining imaging and modelling to reveal positive feedback regulation in GABA signalling, centred around random fluctuations of dynamic microtubules.
Mitchison, T. & Kirschner, M. Dynamic instability of microtubule growth. Nature 312, 237–242 (1984).
Kalab, P., Weis, K. & Heald, R. Visualization of a Ran-GTP gradient in interphase and mitotic Xenopus egg extracts. Science 295, 2452–2456 (2002).
Bastiaens, P., Caudron, M., Niethammer, P. & Karsenti, E. Gradients in the self-organization of the mitotic spindle. Trends Cell Biol. 16, 125–134 (2006).
Caudron, M., Bunt, G., Bastiaens, P. & Karsenti, E. Spatial coordination of spindle assembly by chromosome-mediated signalling gradients. Science 309, 1373–1376 (2005).
Einstein, A. The motion of elements suspended in static liquids as claimed in the molecular kinetic theory of heat. Ann. Phys. 17, 549–560 (1905).
Axelrod, D., Koppel, D. E., Schlessinger, J., Elson, E. & Webb, W. W. Mobility measurement by analysis of fluorescence photobleaching recovery kinetics. Biophys. J. 16, 1055–1069 (1976).
Dunn, G. A., Dobbie, I. M., Monypenny, J., Holt, M. R. & Zicha, D. Fluorescence localization after photobleaching (FLAP): a new method for studying protein dynamics in living cells. J. Microsc. 205, 109–112 (2002).
Patterson, G. H. & Lippincott-Schwartz, J. A photoactivatable GFP for selective photolabelling of proteins and cells. Science 297, 1873–1877 (2002).
Ando, R., Hama, H., Yamamoto-Hino, M., Mizuno, H. & Miyawaki, A. An optical marker based on the UV-induced green-to-red photoconversion of a fluorescent protein. Proc. Natl Acad. Sci. USA 99, 12651–12656 (2002).
Gurskaya, N. G. et al. Engineering of a monomeric green-to-red photoactivatable fluorescent protein induced by blue light. Nature Biotech. 24, 461–465 (2006).
Rocks, O. et al. The palmitoylation machinery is a spatially organizing system for peripheral membrane proteins. Cell 141, 458–471 (2010).
Giordano, L., Jovin, T. M., Irie, M. & Jares-Erijman, E. A. Diheteroarylethenes as thermally stable photoswitchable acceptors in photochromic fluorescence resonance energy transfer (pcFRET). J. Am. Chem. Soc. 124, 7481–7489 (2002).
Ando, R., Mizuno, H. & Miyawaki, A. Regulated fast nucleocytoplasmic shuttling observed by reversible protein highlighting. Science 306, 1370–1373 (2004). Powerful ensemble measurements of protein mobility using the novel fluorescent protein Dronpa, which allowed reversible highlighting and therefore repeated mobility measurements in an individual cell during growth factor stimulation.
Koppel, D. E. & Sheetz, M. P. A localized pattern photobleaching method for the concurrent analysis of rapid and slow diffusion processes. Biophys. J. 43, 175–181 (1983).
Kang, M., Day, C. A., Drake, K., Kenworthy, A. K. & DiBenedetto, E. A generalization of theory for two-dimensional fluorescence recovery after photobleaching applicable to confocal laser scanning microscopes. Biophys. J. 97, 1501–1511 (2009).
Gelles, J., Schnapp, B. J. & Sheetz, M. P. Tracking kinesin-driven movements with nanometre-scale precision. Nature 331, 450–453 (1988).
Anderson, C. M., Georgiou, G. N., Morrison, I. E., Stevenson, G. V. & Cherry, R. J. Tracking of cell surface receptors by fluorescence digital imaging microscopy using a charge-coupled device camera. Low-density lipoprotein and influenza virus receptor mobility at 4°C. J. Cell Sci. 101, 415–425 (1992).
Ghosh, R. N. & Webb, W. W. Automated detection and tracking of individual and clustered cell surface low density lipoprotein receptor molecules. Biophys. J. 66, 1301–1318 (1994).
Dahan, M. et al. Diffusion dynamics of glycine receptors revealed by single-quantum dot tracking. Science 302, 442–445 (2003).
Manley, S. et al. High-density mapping of single-molecule trajectories with photoactivated localization microscopy. Nature Methods 5, 155–157 (2008). Photoswitchable dyes allowed high-density mapping of protein diffusion at subdiffraction resolution.
Suzuki, K., Ritchie, K., Kajikawa, E., Fujiwara, T. & Kusumi, A. Rapid hop diffusion of a G-protein-coupled receptor in the plasma membrane as revealed by single-molecule techniques. Biophys. J. 88, 3659–3680 (2005).
Saxton, M. J. A biological interpretation of transient anomalous subdiffusion. I. Qualitative model. Biophys. J. 92, 1178–1191 (2007).
Ram, S., Prabhat, P., Chao, J., Ward, E. S. & Ober, R. J. High accuracy 3D quantum dot tracking with multifocal plane microscopy for the study of fast intracellular dynamics in live cells. Biophys. J. 95, 6025–43 (2008).
Han, K. Y. et al. Three-dimensional stimulated emission depletion microscopy of nitrogen-vacancy centers in diamond using continuous-wave light. Nano Lett. 9, 3323–3329 (2009).
Batalov, A. et al. Low temperature studies of the excited-state structure of negatively charged nitrogen-vacancy colour centers in diamond. Phys. Rev. Lett. 102, 195506 (2009).
Magde, D., Elson, E., Webb, W. W. Thermodynamic fluctuations in a reacting system—measurement by fluorescence correlation spectroscopy. Phys. Rev. Lett. 29, 705–708 (1972).
Schwille, P., Haupts, U., Maiti, S. & Webb, W. W. Molecular dynamics in living cells observed by fluorescence correlation spectroscopy with one- and two-photon excitation. Biophys. J. 77, 2251–2265 (1999).
Hebert, B., Costantino, S. & Wiseman, P. W. Spatiotemporal image correlation spectroscopy (STICS) theory, verification, and application to protein velocity mapping in living CHO cells. Biophys. J. 88, 3601–3614 (2005).
Digman, M. A. et al. Fluctuation correlation spectroscopy with a laser-scanning microscope: exploiting the hidden time structure. Biophys. J. 88, L33–L36 (2005).
Danuser, G. & Waterman-Storer, C. M. Quantitative fluorescent speckle microscopy of cytoskeleton dynamics. Annu. Rev. Biophys. Biomol. Struct. 35, 361–387 (2006). A detailed review on quantitative speckle microscopy, discussing advantages and limits of FSM versus single molecule tracking and discussing several applications in studying cytoskeletal organization.
Waterman-Storer, C. M., Desai, A., Bulinski, J. C. & Salmon, E. D. Fluorescent speckle microscopy, a method to visualize the dynamics of protein assemblies in living cells. Curr. Biol. 8, 1227–1230 (1998).
Watanabe, N. & Mitchison, T. J. Single-molecule speckle analysis of actin filament turnover in lamellipodia. Science 295, 1083–1086 (2002). Single green fluorescent protein-labelled actin molecules were analysed by speckle microscopy in living cells.
Grecco, H. E. &. Bastiaens, P. I. H. in Live Cell Imaging: a Laboratory Manual (eds Goldman R. D. et al.) (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 2010).
Förster, T. Zwischenmolekulare Energiewanderung und Fluoreszenz. Ann. Phys. 437, 55–75 (1948) (in German).
Gordon, G. W., Berry, G., Liang, X. H., Levine, B. & Herman, B. Quantitative fluorescence resonance energy transfer measurements using fluorescence microscopy. Biophys. J. 74, 2702–2713 (1998).
Mahajan, N. P., Harrison-Shostak, D. C., Michaux, J. & Herman, B. Novel mutant green fluorescent protein protease substrates reveal the activation of specific caspases during apoptosis. Chem. Biol. 6, 401–409 (1999).
Bastiaens, P. I., Majoul, I. V., Verveer, P. J., Soling, H. D. & Jovin, T. M. Imaging the intracellular trafficking and state of the AB5 quaternary structure of cholera toxin. EMBO J. 15, 4246–4253 (1996).
Lakowicz, J. R., Szmacinski, H., Nowaczyk, K. & Johnson, M. L. Fluorescence lifetime imaging of free and protein-bound NADH. Proc. Natl Acad. Sci. USA 89, 1271–1275 (1992).
Gadella, T. W. Jr & Jovin, T. M. Oligomerization of epidermal growth factor receptors on A431 cells studied by time-resolved fluorescence imaging microscopy. A stereochemical model for tyrosine kinase receptor activation. J. Cell Biol. 129, 1543–1558 (1995).
Verveer, P. J., Squire, A. & Bastiaens, P. I. Global analysis of fluorescence lifetime imaging microscopy data. Biophys. J. 78, 2127–2137 (2000).
Verveer, P. J., Wouters, F. S., Reynolds, A. R. & Bastiaens, P. I. Quantitative imaging of lateral ErbB1 receptor signal propagation in the plasma membrane. Science 290, 1567–1570 (2000).
Adams, S. R., Harootunian, A. T., Buechler, Y. J., Taylor, S. S. & Tsien, R. Y. Fluorescence ratio imaging of cyclic AMP in single cells. Nature 349, 694–697 (1991).
Itoh, R. E. et al. Activation of Rac and Cdc42 video imaged by fluorescent resonance energy transfer-based single-molecule probes in the membrane of living cells. Mol. Cell. Biol. 22, 6582–6591 (2002).
Offterdinger, M., Georget, V., Girod, A. & Bastiaens, P. I. Imaging phosphorylation dynamics of the epidermal growth factor receptor. J. Biol. Chem. 279, 36972–36981 (2004).
Mochizuki, N. et al. Spatio-temporal images of growth-factor-induced activation of Ras and Rap1. Nature 411, 1065–1068 (2001).
Pertz, O., Hodgson, L., Klemke, R. L. & Hahn, K. M. Spatiotemporal dynamics of RhoA activity in migrating cells. Nature 440, 1069–1072 (2006).
Niethammer, P., Bastiaens, P. & Karsenti, E. Stathmin-tubulin interaction gradients in motile and mitotic cells. Science 303, 1862–1866 (2004).
Hahn, K., DeBiasio, R. & Taylor, D. L. Patterns of elevated free calcium and calmodulin activation in living cells. Nature 359, 736–738 (1992).
Nalbant, P., Hodgson, L., Kraynov, V., Toutchkine, A. & Hahn, K. M. Activation of endogenous Cdc42 visualized in living cells. Science 305, 1615–1619 (2004).
Machacek, M. et al. Coordination of Rho GTPase activities during cell protrusion. Nature 461, 99–103 (2009). A combination of two biosensor concepts and computationally assisted correlation based on cellular protrusion dynamics enabled the comparative analysis of activation dynamics of three Rho GTPases.
Baird, G. S., Zacharias, D. A. & Tsien, R. Y. Circular permutation and receptor insertion within green fluorescent proteins. Proc. Natl Acad. Sci. USA 96, 11241–11246 (1999).
Belousov, V. V. et al. Genetically encoded fluorescent indicator for intracellular hydrogen peroxide. Nature Methods 3, 281–286 (2006).
Berg, J., Hung., Y. P. & Yellen, G. A genetically encoded fluorescent reporter of ATP:ADP ratio. Nature Methods 6, 161–166 (2009).
Parent, C. A., Blacklock, B. J., Froehlich, W. M., Murphy, D. B. & Devreotes, P. N. G protein signalling events are activated at the leading edge of chemotactic cells. Cell 95, 81–91 (1998).
Meili, R. et al. Chemoattractant-mediated transient activation and membrane localization of Akt/PKB is required for efficient chemotaxis to cAMP in Dictyostelium. EMBO J. 18, 2092–2105 (1999).
Servant, G. et al. Polarization of chemoattractant receptor signalling during neutrophil chemotaxis. Science 287, 1037–1040 (2000).
Ting, A. Y., Kain, K. H., Klemke, R. L. & Tsien, R. Y. Genetically encoded fluorescent reporters of protein tyrosine kinase activities in living cells. Proc. Natl Acad. Sci. USA 98, 15003–15008 (2001).
Violin, J. D., Zhang, J., Tsien, R. Y. & Newton, A. C. A genetically encoded fluorescent reporter reveals oscillatory phosphorylation by protein kinase C. J. Cell Biol. 161, 899–909 (2003).
Xu, X. et al. Detection of programmed cell death using fluorescence energy transfer. Nucleic Acids Res. 26, 2034–2035 (1998).
Harpur, A. G., Wouters, F. S. & Bastiaens, P. I. Imaging FRET between spectrally similar GFP molecules in single cells. Nature Biotech. 19, 167–169 (2001).
Wichmann, O., Wittbrodt, J. & Schultz, C. A small-molecule FRET probe to monitor phospholipase A2 activity in cells and organisms. Angew. Chem. Int. Ed Engl. 45, 508–512 (2006).
Yudushkin, I. A. et al. Live-cell imaging of enzyme-substrate interaction reveals spatial regulation of PTP1B. Science 315, 115–119 (2007). Direct observation of enzyme–substrate complexes by FLIM measurements of FRET allow spatial mapping of enzyme kinetic parameters in cells.
Tyson, J. J., Chen, K. C. & Novak, B. Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signalling pathways in the cell. Curr. Opin. Cell Biol. 15, 221–231 (2003). A detailed review discussing how the topology of signal networks influences their response to inputs.
Ferrell, J. E. Jr. Tripping the switch fantastic: how a protein kinase cascade can convert graded inputs into switch-like outputs. Trends Biochem. Sci. 21, 460–466 (1996).
Ferrell, J. E., Jr. & Machleder, E. M. The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes. Science 280, 895–898 (1998).
Kholodenko, B. N. Cell-signalling dynamics in time and space. Nature Rev. Mol. Cell Biol. 7, 165–176 (2006).
Santos, S. D. M., Verveer, P. J. & Bastiaens, P. I. H. Growth factor-induced MAPK network topology shapes Erk response determining PC-12 cell fate. Nature Cell Biol. 9, 324–330 (2007).
Murphy, L. O., Smith, S., Chen, R. H., Fingar, D. C. & Blenis, J. Molecular interpretation of ERK signal duration by immediate early gene products. Nature Cell Biol. 4, 556–564 (2002).
Laslo, P. et al. Multilineage transcriptional priming and determination of alternate haematopoietic cell fates. Cell 126, 755–766 (2006).
Xiong, W. & Ferrell, J. E. Jr. A positive-feedback-based bistable 'memory module' that governs a cell fate decision. Nature 426, 460–465 (2003).
Ingolia, N. T. Topology and robustness in the Drosophila segment polarity network. PLoS Biol. 2, 805–815 (2004).
Niethammer, P. et al. Discrete states of a protein interaction network govern interphase and mitotic microtubule dynamics. PLoS Biol. 5, 190–202 (2007).
Brown, G. C. & Kholodenko, B. N. Spatial gradients of cellular phospho-proteins. FEBS Lett. 457, 452–454 (1999).
Hyman, A. A. & Karsenti, E. Morphogenetic properties of microtubules and mitotic spindle assembly. Cell 84, 401–410 (1996). The first discussion of the existence of intracellular activity gradients that have a role in spindle morphogenesis.
Kalab, P., Pralle, A., Isacoff, E. Y., Heald, R. & Weis, K. Analysis of a RanGTP-regulated gradient in mitotic somatic cells. Nature 440, 697–701 (2006).
Wollman, R. et al. Efficient chromosome capture requires a bias in the 'search-and-capture' process during mitotic-spindle assembly. Curr. Biol. 15, 828–832 (2005).
Andersen, S. S. et al. Mitotic chromatin regulates phosphorylation of stathmin/OP18. Nature 389, 640–643 (1997).
Tournebize, R. et al. Distinct roles of PP1 and PP2A-like phosphatases in control of microtubule dynamics during mitosis. EMBO J. 16, 5537–5549 (1997).
Fuller, B. G. et al. Midzone activation of aurora B in anaphase produces an intracellular phosphorylation gradient. Nature 453, 1132–1136 (2008).
Maeder, C. I. et al. Spatial regulation of Fus3 MAP kinase activity through a reaction-diffusion mechanism in yeast pheromone signalling. Nature Cell Biol. 9, 1319–1326 (2007).
Moseley, J. B., Mayeux, A., Paoletti, A. & Nurse, P. A spatial gradient coordinates cell size and mitotic entry in fission yeast. Nature 459, 857–860 (2009).
Coppey, M., Boettiger, A. N., Berezhkovskii, A. M. & Shvartsman, S. Y. Nuclear trapping shapes the terminal gradient in the Drosophila embryo. Curr. Biol. 18, 915–919 (2008).
Pollard, T. D. & Borisy, G. G. Cellular motility driven by assembly and disassembly of actin filaments. Cell 112, 453–465 (2003).
Walczak, C. E. & Heald, R. Mechanisms of mitotic spindle assembly and function. Int. Rev. Cytol. 265, 111–158 (2008).
Karsenti, E. Self-organization in cell biology: a brief history. Nature Rev. Mol. Cell Biol. 9, 255–262 (2008). An insightful article about the history of the concepts of intracellular self-organization.
Kikkawa, M., Ishikawa, T., Wakabayashi, T. & Hirokawa, N. Three-dimensional structure of the kinesin head-microtubule complex. Nature 376, 274–277 (1995).
Hirose, K., Lockhart, A., Cross, R. A. & Amos, L. A. Three-dimensional cryoelectron microscopy of dimeric kinesin and ncd motor domains on microtubules. Proc. Natl Acad. Sci. USA 93, 9539–9544 (1996).
Turing, A. M. The chemical basis of morphogenesis. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 237, 37–72 (1952).
Nagorcka, B. N. Wavelike isomorphic prepatterns in development. J. Theor. Biol. 137, 127–162 (1989).
Murray, J. D. A pre-pattern formation mechanism for animal coat markings. J. Theor. Biol. 88, 161–199 (1981).
A. G. Searle. Comparative Genetics of Coat Colour in Mammals. (Logos Press, London; Academic Press, New York, 1968).
Keilhack, H. et al. Phosphotyrosine 1173 mediates binding of the protein-tyrosine phosphatase SHP-1 to the epidermal growth factor receptor and attenuation of receptor signalling. J. Biol. Chem. 273, 24839–24846 (1998).
Frank, C. et al. Effective dephosphorylation of Src substrates by SHP-1. J. Biol. Chem. 279, 11375–11383 (2004).
Uchida, T. et al. Insulin stimulates the phosphorylation of Tyr538 and the catalytic activity of PTP1C, a protein tyrosine phosphatase with Src homology-2 domains. J. Biol. Chem. 269, 12220–8 (1994).
Gierer, A. & Meinhardt, H. A theory of biological pattern formation. Kybernetik 12, 30–39 (1972).
Goryachev, A. B. & Pokhilko, A. V. Dynamics of Cdc42 network embodies a Turing-type mechanism of yeast cell polarity. FEBS Lett. 582, 1437–1443 (2008).
Meinhardt, H. Models for organizer and notochord formation. C R. Acad. Sci. III 323, 23–30 (2000).
Wong, K., Pertz, O., Hahn, K. & Bourne, H. Neutrophil polarization: spatiotemporal dynamics of RhoA activity support a self-organizing mechanism. Proc. Natl Acad. Sci. USA 103, 3639–3644 (2006).
Xu, J. et al. Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. Cell 114, 201–214 (2003).
Narang, A. Spontaneous polarization in eukaryotic gradient sensing: a mathematical model based on mutual inhibition of frontness and backness pathways. J. Theor. Biol. 240, 538–553 (2006).
Onsum, M. & Rao, C. V. A mathematical model for neutrophil gradient sensing and polarization. PLoS Comput. Biol. 3, 436–450 (2007).
Verkhovsky, A. B., Svitkina, T. M. & Borisy, G. G. Self-polarization and directional motility of cytoplasm. Curr. Biol. 9, 11–20 (1999).
Tabony, J. Microtubules viewed as molecular ant colonies. Biol. Cell 98, 603–617 (2006).
Dumont, S. & Mitchison, T. J. Force and length in the mitotic spindle. Curr. Biol. 19, R749–R761 (2009).
Howard, J. Mechanical signalling in networks of motor and cytoskeletal proteins. Annu. Rev. Biophys. 38, 217–234 (2009).
Nedelec, F. J., Surrey, T., Maggs, A. C. & Leibler, S. Self-organization of microtubules and motors. Nature 389, 305–308 (1997).
Surrey, T., Nedelec, F., Leibler, S. & Karsenti, E. Physical properties determining self-organization of motors and microtubules. Science 292, 1167–1171 (2001). Spontaneous aster formation from artificially cross-linked molecular motors and dynamically growing microtubules is reconstituted in vitro using purified components and resulting structures are compared with computational simulations.
Dehmelt, L., Nalbant, P., Steffen, W. & Halpain, S. A microtubule-based, dynein-dependent force induces local cell protrusions: implications for neurite initiation. Brain Cell Biol. 35, 39–56 (2006).
Tischer, C. & Bastiaens, P. I. Lateral phosphorylation propagation: an aspect of feedback signalling? Nature Rev. Mol. Cell Biol. 4, 971–974 (2003).
Arrio-Dupont, M., Foucault, G., Vacher, M., Devaux, P. F. & Cribier, S. Translational diffusion of globular proteins in the cytoplasm of cultured muscle cells. Biophys. J. 78, 901–907 (2000).
Caviston, J. P. & Holzbaur, E. L. Microtubule motors at the intersection of trafficking and transport. Trends Cell Biol. 16, 530–537 (2006).
Charras, G. T., Mitchison, T. J. & Mahadevan, L. Animal cell hydraulics. J. Cell Sci. 122, 3233–3241 (2009).
Hodgkin, A. L. & Huxley, A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. 117, 500–544 (1952).
Dawson, S. P., Keizer, J. & Pearson, J. E. Fire-diffuse-fire model of dynamics of intracellular calcium waves. Proc. Natl Acad. Sci. USA 96, 6060–6063 (1999).
Sawano, A., Takayama, S., Matsuda, M. & Miyawaki, A. Lateral propagation of EGF signalling after local stimulation is dependent on receptor density. Dev. Cell 3, 245–257 (2002).
We thank the following colleagues from our department: A. Kraemer for help in preparing the manuscript, A. Chandra for providing the microscopic images in Figure 2a and M. Schmick for providing the cellular automaton simulation.
The authors declare no competing financial interests.
- Dissipative system
A dynamic system that operates far out of equilibrium and exchanges energy and matter with its environment.
Derived from the Greek 'stigma', meaning mark or sign, and 'ergon', meaning work or action. This concept was used to describe termite mound construction, in which the work in progress provides marks for further work.
- Cytoplasmic state
One of a limited number of dynamically maintained, inter-converting states of an intracellular signalling network that define distinct cellular behaviours.
- Fluorescence photobleaching
Irreversible photo-destruction of fluorescent molecules by prolonged and/or intense illumination.
- Quantum dots
Inorganic, semi-conductor crystals, which are used as alternatives to organic fluorophore dyes owing to their bright fluorescence and high photostability
- Diffraction pattern
A pattern, forming by constructive and destructive interference, that occurs if waves encounter an obstacle or a medium with varying refractive index. The interference pattern sets a limit to resolve two closely spaced structures by optical methods.
- Total internal reflection fluorescence microscopy
A microscopy method in which total reflection is used to generate an exponentially decaying evanescent wave at a glass–water interface, with a depth of 50–300 nm, to selectively excite fluorescent molecules near a surface.
- Multifocal plane microscopy
An extension to standard microscopy techniques in which multiple images at distinct focal planes are recorded simultaneously to allow the accurate positioning of particles in 3D.
- Fluorescence correlation spectroscopy
A microscopic method to measure diffusion coefficients and concentrations of fluorescent molecules by detecting their passage through a small volume generated by the focus of a confocal microscope.
- Fluorescence speckle microscopy
A microscopy method to determine protein mobilities by substochiometric fluorescent labelling of intracellular supramolecular structures.
The part of a molecule that absorbs visible light and thereby provides colour to the molecule. If the molecule re-emits excited-state energy as light, it is also a fluorophore.
- Acceptor-sensitized emission
Fluorescence emission of an acceptor fluorophore that is excited by FRET.
- Fluorescence lifetime imaging microscopy
A microscopy method to image the excited state lifetimes of fluorophores.
- Solvatochromic dye
A fluorophore that changes its spectral properties owing to a change in solvent polarity.
- Michaelis constant
The substrate concentration at which the rate of an enzymatic reaction (that is governed by Michaelis–Menten kinetics) is at half of its maximal value.
- Michaelis–Menten kinetics
A widespread model for saturable enzyme kinetics, described in Michaelis, L., Menten, M. L. Biochem. Z. 49, 333–369 (1913).
A path-dependent lag in a dynamic process, which leads to an asymmetry in forward and backward transitions.
A tip structure (named after a cartoon character) involved in cell fusion of mating yeast that emerges after pheromone stimulation.
- Hydrodynamic radius
The radius of a hypothetical solid sphere that has the theoretical diffusional mobility of a measured particle in a given solvent.
The star-shaped geometric arrangement of filaments.
About this article
Cite this article
Dehmelt, L., Bastiaens, P. Spatial organization of intracellular communication: insights from imaging. Nat Rev Mol Cell Biol 11, 440–452 (2010). https://doi.org/10.1038/nrm2903
Nature Reviews Methods Primers (2021)
Nature Communications (2021)
Highly chemiluminescent TiO2/tetra(4-carboxyphenyl)porphyrin/N-(4-aminobutyl)-N-ethylisoluminol nanoluminophores for detection of heart disease biomarker copeptin based on chemiluminescence resonance energy transfer
Analytical and Bioanalytical Chemistry (2019)
Nature Neuroscience (2018)
Nature Reviews Molecular Cell Biology (2017)