|
Copyright © 2005 by the National Academy of Sciences.
Diffusion-limited phase separation in eukaryotic chemotaxis
Andrea Gamba *,
*Department of Mathematics, Polytechnic of Torino, 10129 Turin, Italy; Accepted for publication September 14, 2005. Received for publication May 12, 2005. Abstract: 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 (PIP3) on the plasma membrane side exposed to the highest chemoattractant concentration, whereas PIP3-degrading enzyme PTEN and its product PIP2 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.
Key Words: directional sensing • lattice model • first-order phase transitions
Author contributions: A.G., A.d.C., S.D.T., A.C., F.B., and G.S. designed research, performed research, analyzed data, and wrote the paper. Conflict of interest statement: No conflicts declared. This paper was submitted directly (Track II) to the PNAS office. Abbreviations: PI3K, phosphatidylinositol 3-kinase; PIP3, D3-phosphoinositide product of PI3K.
The editors suggest the following Related Resources on Science sites:In Science Signaling
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
|
,
Antonio de Candia 
,
Stefano Di Talia 
,
Antonio Coniglio 
To whom correspondence may be addressed. E-mail: 
Science Signaling. ISSN 1937-9145 (pre-2008: Science's STKE. ISSN 1525-8882)
Magazine | News | Signaling | Careers | Multimedia | Collections | Help | Site Map | RSS
Subscribe | Feedback | Privacy / Legal | About Us | Advertise With Us | Contact Us
© 2005 American Association for the Advancement of Science. All Rights Reserved.
AAAS is a partner of HINARI, AGORA, PatientInform, CrossRef, and COUNTER.
You have reached the bottom of the page. Back to top