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A bistable model of cell polarity.

Semplice M, Veglio A, Naldi G, Serini G, Gamba A - PLoS ONE (2012)

Bottom Line: Cell membrane polarization is a fundamental process implicated in several basic biological phenomena, such as differentiation, proliferation, migration and morphogenesis of unicellular and multicellular organisms.We describe a simple, solvable model of cell membrane polarization based on the coupling of membrane diffusion with bistable enzymatic dynamics.The model can reproduce a broad range of symmetry-breaking events, such as those observed in eukaryotic directional sensing, the apico-basal polarization of epithelium cells, the polarization of budding and mating yeast, and the formation of Ras nanoclusters in several cell types.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics and Mathematics, Università dell'Insubria, Como, Italy.

ABSTRACT
Ultrasensitivity, as described by Goldbeter and Koshland, has been considered for a long time as a way to realize bistable switches in biological systems. It is not as well recognized that when ultrasensitivity and reinforcing feedback loops are present in a spatially distributed system such as the cell plasmamembrane, they may induce bistability and spatial separation of the system into distinct signaling phases. Here we suggest that bistability of ultrasensitive signaling pathways in a diffusive environment provides a basic mechanism to realize cell membrane polarity. Cell membrane polarization is a fundamental process implicated in several basic biological phenomena, such as differentiation, proliferation, migration and morphogenesis of unicellular and multicellular organisms. We describe a simple, solvable model of cell membrane polarization based on the coupling of membrane diffusion with bistable enzymatic dynamics. The model can reproduce a broad range of symmetry-breaking events, such as those observed in eukaryotic directional sensing, the apico-basal polarization of epithelium cells, the polarization of budding and mating yeast, and the formation of Ras nanoclusters in several cell types.

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Related in: MedlinePlus

Kimograph for a simulation of the full, spatially distributed, chemotaxis system.In the simulation, before starting to stimulate cells with a uniform concentration of cAMP, the system is left to relax with zero signal until the levels of the relevant factors become stationary. Then, the stimulation is switched on at time , when we also impose a gaussian noise on the uniform concentration background in order to mimick random inhomogeneities. We compare the experimental results reported in Reference [19] with the simulations of model (1–8). The kimograph shows the time evolution of simulated PIP3 levels along the major cell perimeter. Time  in the simulation is to be compared with time  s in the experiment.
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pone-0030977-g008: Kimograph for a simulation of the full, spatially distributed, chemotaxis system.In the simulation, before starting to stimulate cells with a uniform concentration of cAMP, the system is left to relax with zero signal until the levels of the relevant factors become stationary. Then, the stimulation is switched on at time , when we also impose a gaussian noise on the uniform concentration background in order to mimick random inhomogeneities. We compare the experimental results reported in Reference [19] with the simulations of model (1–8). The kimograph shows the time evolution of simulated PIP3 levels along the major cell perimeter. Time in the simulation is to be compared with time s in the experiment.

Mentions: In order to validate the present scenario we have simulated the full, spatially distributed system (1–8) by using a finite-element method, with and other parameters values reported from the literature (Table 2). Thermal and chemical reaction noise is taken into account by adding an additive random perturbation in the r.h.s. of (1, 2) (see Methods). Noise has the effect of creating germs of the PIP3-rich phase as localized, rare concentration fluctuations. In the simulation, before starting to stimulate cells with a uniform concentration of cAMP, the system is left to relax with zero signal until the levels of the relevant factors become stationary and the cell membrane becomes uniformly covered by the PIP2-rich phase (blue, Fig. 8b). The stimulation is switched on at time , when we also impose a 5% Gaussian noise on the uniform concentration background in order to mimick random inhomogeneities. In Fig. 8 we compare the experimental results reported in Ref. [19] with the simulations of model (1–8).


A bistable model of cell polarity.

Semplice M, Veglio A, Naldi G, Serini G, Gamba A - PLoS ONE (2012)

Kimograph for a simulation of the full, spatially distributed, chemotaxis system.In the simulation, before starting to stimulate cells with a uniform concentration of cAMP, the system is left to relax with zero signal until the levels of the relevant factors become stationary. Then, the stimulation is switched on at time , when we also impose a gaussian noise on the uniform concentration background in order to mimick random inhomogeneities. We compare the experimental results reported in Reference [19] with the simulations of model (1–8). The kimograph shows the time evolution of simulated PIP3 levels along the major cell perimeter. Time  in the simulation is to be compared with time  s in the experiment.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3285628&req=5

pone-0030977-g008: Kimograph for a simulation of the full, spatially distributed, chemotaxis system.In the simulation, before starting to stimulate cells with a uniform concentration of cAMP, the system is left to relax with zero signal until the levels of the relevant factors become stationary. Then, the stimulation is switched on at time , when we also impose a gaussian noise on the uniform concentration background in order to mimick random inhomogeneities. We compare the experimental results reported in Reference [19] with the simulations of model (1–8). The kimograph shows the time evolution of simulated PIP3 levels along the major cell perimeter. Time in the simulation is to be compared with time s in the experiment.
Mentions: In order to validate the present scenario we have simulated the full, spatially distributed system (1–8) by using a finite-element method, with and other parameters values reported from the literature (Table 2). Thermal and chemical reaction noise is taken into account by adding an additive random perturbation in the r.h.s. of (1, 2) (see Methods). Noise has the effect of creating germs of the PIP3-rich phase as localized, rare concentration fluctuations. In the simulation, before starting to stimulate cells with a uniform concentration of cAMP, the system is left to relax with zero signal until the levels of the relevant factors become stationary and the cell membrane becomes uniformly covered by the PIP2-rich phase (blue, Fig. 8b). The stimulation is switched on at time , when we also impose a 5% Gaussian noise on the uniform concentration background in order to mimick random inhomogeneities. In Fig. 8 we compare the experimental results reported in Ref. [19] with the simulations of model (1–8).

Bottom Line: Cell membrane polarization is a fundamental process implicated in several basic biological phenomena, such as differentiation, proliferation, migration and morphogenesis of unicellular and multicellular organisms.We describe a simple, solvable model of cell membrane polarization based on the coupling of membrane diffusion with bistable enzymatic dynamics.The model can reproduce a broad range of symmetry-breaking events, such as those observed in eukaryotic directional sensing, the apico-basal polarization of epithelium cells, the polarization of budding and mating yeast, and the formation of Ras nanoclusters in several cell types.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics and Mathematics, Università dell'Insubria, Como, Italy.

ABSTRACT
Ultrasensitivity, as described by Goldbeter and Koshland, has been considered for a long time as a way to realize bistable switches in biological systems. It is not as well recognized that when ultrasensitivity and reinforcing feedback loops are present in a spatially distributed system such as the cell plasmamembrane, they may induce bistability and spatial separation of the system into distinct signaling phases. Here we suggest that bistability of ultrasensitive signaling pathways in a diffusive environment provides a basic mechanism to realize cell membrane polarity. Cell membrane polarization is a fundamental process implicated in several basic biological phenomena, such as differentiation, proliferation, migration and morphogenesis of unicellular and multicellular organisms. We describe a simple, solvable model of cell membrane polarization based on the coupling of membrane diffusion with bistable enzymatic dynamics. The model can reproduce a broad range of symmetry-breaking events, such as those observed in eukaryotic directional sensing, the apico-basal polarization of epithelium cells, the polarization of budding and mating yeast, and the formation of Ras nanoclusters in several cell types.

Show MeSH
Related in: MedlinePlus