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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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Growth of the PIP2-rich phase (blue lower patch).The color scale shows the gradation of PIP2 content: the color is the relative concentration difference between PIP3 and PIP2 at a given site. The system at initial time is in a uniform PIP3-rich phase (red), apart from an initial PIP2-rich seed germ of size larger than the threshold radius. Then, a PIP2-rich patch becomes apparent and its radius saturates to an equilibrium value.
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pone-0030977-g011: Growth of the PIP2-rich phase (blue lower patch).The color scale shows the gradation of PIP2 content: the color is the relative concentration difference between PIP3 and PIP2 at a given site. The system at initial time is in a uniform PIP3-rich phase (red), apart from an initial PIP2-rich seed germ of size larger than the threshold radius. Then, a PIP2-rich patch becomes apparent and its radius saturates to an equilibrium value.

Mentions: Patches smaller than a threshold radius are dissolved by diffusion and thermal processes and do not impair the stability of the uniform PIP3-rich phase. Patches larger than grow in time triggering the separation of the plasmamembrane surface in a PIP2-rich and a PIP3-rich region, and eventually reach an equilibrium, thus completing the separation into a PIP2-rich apical region and a PIP3-rich basolateral region (Fig. 11 and Ref. [37]). The critical radius for nucleation and the final PIP-patch size are functions of the PI3K/PTEN ratio [37]. This fact suggests that the precise amount of PI3K and PTEN is a critical parameter for the establishement of epithelial polarity, providing an explanation for the experimental observation that deletion of a single PTEN allele can interfere with epithelial cell polarization and foster invasion of carcinoma cells [40].


A bistable model of cell polarity.

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

Growth of the PIP2-rich phase (blue lower patch).The color scale shows the gradation of PIP2 content: the color is the relative concentration difference between PIP3 and PIP2 at a given site. The system at initial time is in a uniform PIP3-rich phase (red), apart from an initial PIP2-rich seed germ of size larger than the threshold radius. Then, a PIP2-rich patch becomes apparent and its radius saturates to an equilibrium value.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0030977-g011: Growth of the PIP2-rich phase (blue lower patch).The color scale shows the gradation of PIP2 content: the color is the relative concentration difference between PIP3 and PIP2 at a given site. The system at initial time is in a uniform PIP3-rich phase (red), apart from an initial PIP2-rich seed germ of size larger than the threshold radius. Then, a PIP2-rich patch becomes apparent and its radius saturates to an equilibrium value.
Mentions: Patches smaller than a threshold radius are dissolved by diffusion and thermal processes and do not impair the stability of the uniform PIP3-rich phase. Patches larger than grow in time triggering the separation of the plasmamembrane surface in a PIP2-rich and a PIP3-rich region, and eventually reach an equilibrium, thus completing the separation into a PIP2-rich apical region and a PIP3-rich basolateral region (Fig. 11 and Ref. [37]). The critical radius for nucleation and the final PIP-patch size are functions of the PI3K/PTEN ratio [37]. This fact suggests that the precise amount of PI3K and PTEN is a critical parameter for the establishement of epithelial polarity, providing an explanation for the experimental observation that deletion of a single PTEN allele can interfere with epithelial cell polarization and foster invasion of carcinoma cells [40].

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