Abstract
Eukaryotic cells are able to sense spatial gradients of chemotactic signal.
This ability governs the development of complex eukaryotic organisms.
Experiments show that cells exposed to shallow chemoattractant
gradients respond with strong accumulation of the phosphatidylinositol
3-kinase (PI3K) enzyme and its phosphoinositide product PIP3 on the plasma
membrane side exposed to the highest chemoattractant concentration 1,
whereas the PIP3-degrading enzyme PTEN and its product PIP2 localize in a
complementary pattern. In physical terms, the process of directional
sensing shows the characteristic phenomenology of phase separation 2,3. We
propose a simple model which reproduces the main features of this
process. The phosphoinositide species PIP2 and PIP3 are represented as
states of an Ising spin and the chemoattractant signal plays the role
of external field. The state of cells exposed to a uniform
chemoattractant activation field is described as a metastable, uniform PIP3-rich state.
The system dynamics leads to formation of PIP2 patches in
the PIP3 sea and to a coarsening process culminating in the formation of two
large domains, respectively rich in PIP2 and PIP3. In the presence of a
uniform activation field the coarsening process is completely random, the
size of PIP2 patches grows in time $t$ approximately as $t^1/2$, and the
polarization process completes in a time $t_\astR^2$, where $R$ is
the size of the system. In the presence of a slight anisotropic component
$\epsilon$ in the activation field the process is completed after a time
$t_\epsilon$, which can be much faster than $t_\ast$, thus leading to an
effective amplification of the slight anisotropic component in the
chemotactic signal. A threshold in the steepness of the smallest
detectable anisotropic component is observed, along with a loss in
sensitivity at higher concentrations of chemotactic signal, in agreement
with recent experimental findings 4.\\
1) C. Janetopoulos, L. Ma, P. N. Nevreotes, P. A. Iglesias Natl. Acad. Sci U.S.A. 101, 16606 (2004).\\
2) A. Gamba, A.de Candia, A.Coniglio, F. Bussolino, G. Serini Proc. Natl. Acad. Sci U.S.A. 102, 16927 (2005).\\
3) A. Gamba, A.de Candia, A.Coniglio, F. Bussolino, G. Serini Sci. STKE 378 (2007), pl1.\\
4) L. Song, S. M. Nadkarni, H. U. Bodeker, C. Beta, A. Bae, C. Frank, W. J. Rappel, W.F. Loomis, E. Bodenschatz, Eur. J. Cell Biol. 85, 981 (2006).
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