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Spatial organization of intracellular communication: insights from imaging

Key Points

  • 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.

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Figure 1: Comparison of macroscopic and microscopic self-organization.
Figure 2: Measurement of protein mobility in cells.
Figure 3: Measurement of protein reactions in cells.
Figure 4: Kinase–phosphatase reaction cycles.
Figure 5: Gradients generate local cytoplasmic states, which steer morphological processes.
Figure 6: Self-organization in intracellular pattern formation and structural growth processes.


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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.

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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.

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Dehmelt, L., Bastiaens, P. Spatial organization of intracellular communication: insights from imaging. Nat Rev Mol Cell Biol 11, 440–452 (2010).

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