Skip to main content
Journal cover image

Diffusion-limited phase separation in eukaryotic chemotaxis.

Publication ,  Journal Article
Gamba, A; de Candia, A; Di Talia, S; Coniglio, A; Bussolino, F; Serini, G
Published in: Proc Natl Acad Sci U S A
November 22, 2005

The ability of cells to sense spatial gradients of chemoattractant factors governs the development of complex eukaryotic organisms. Cells exposed to shallow chemoattractant gradients respond with strong accumulation of the enzyme phosphatidylinositol 3-kinase (PI3K) and its D3-phosphoinositide product (PIP(3)) on the plasma membrane side exposed to the highest chemoattractant concentration, whereas PIP(3)-degrading enzyme PTEN and its product PIP(2) localize in a complementary pattern. Such an early symmetry-breaking event is a mandatory step for directed cell movement elicited by chemoattractants, but its physical origin is still mysterious. Here, we propose that directional sensing is the consequence of a phase-ordering process mediated by phosphoinositide diffusion and driven by the distribution of chemotactic signal. By studying a realistic reaction-diffusion lattice model that describes PI3K and PTEN enzymatic activity, recruitment to the plasma membrane, and diffusion of their phosphoinositide products, we show that the effective enzyme-enzyme interaction induced by catalysis and diffusion introduces an instability of the system toward phase separation for realistic values of physical parameters. In this framework, large reversible amplification of shallow chemotactic gradients, selective localization of chemical factors, macroscopic response timescales, and spontaneous polarization arise naturally. The model is robust with respect to order-of-magnitude variations of the parameters.

Duke Scholars

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

November 22, 2005

Volume

102

Issue

47

Start / End Page

16927 / 16932

Location

United States

Related Subject Headings

  • Stochastic Processes
  • Phosphatidylinositols
  • Phosphatidylinositol 3-Kinases
  • PTEN Phosphohydrolase
  • Models, Biological
  • Membranes, Artificial
  • Eukaryotic Cells
  • Computer Simulation
  • Chemotaxis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gamba, A., de Candia, A., Di Talia, S., Coniglio, A., Bussolino, F., & Serini, G. (2005). Diffusion-limited phase separation in eukaryotic chemotaxis. Proc Natl Acad Sci U S A, 102(47), 16927–16932. https://doi.org/10.1073/pnas.0503974102
Gamba, Andrea, Antonio de Candia, Stefano Di Talia, Antonio Coniglio, Federico Bussolino, and Guido Serini. “Diffusion-limited phase separation in eukaryotic chemotaxis.Proc Natl Acad Sci U S A 102, no. 47 (November 22, 2005): 16927–32. https://doi.org/10.1073/pnas.0503974102.
Gamba A, de Candia A, Di Talia S, Coniglio A, Bussolino F, Serini G. Diffusion-limited phase separation in eukaryotic chemotaxis. Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):16927–32.
Gamba, Andrea, et al. “Diffusion-limited phase separation in eukaryotic chemotaxis.Proc Natl Acad Sci U S A, vol. 102, no. 47, Nov. 2005, pp. 16927–32. Pubmed, doi:10.1073/pnas.0503974102.
Gamba A, de Candia A, Di Talia S, Coniglio A, Bussolino F, Serini G. Diffusion-limited phase separation in eukaryotic chemotaxis. Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):16927–16932.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

November 22, 2005

Volume

102

Issue

47

Start / End Page

16927 / 16932

Location

United States

Related Subject Headings

  • Stochastic Processes
  • Phosphatidylinositols
  • Phosphatidylinositol 3-Kinases
  • PTEN Phosphohydrolase
  • Models, Biological
  • Membranes, Artificial
  • Eukaryotic Cells
  • Computer Simulation
  • Chemotaxis