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Biophys J, September 2001, p. 1314-1323, Vol. 81, No. 3
Groningen Biomolecular Sciences and Biotechnology Institute, Department of Biochemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands
Small chemotactic cells like Dictyostelium
and neutrophils transduce shallow spatial chemoattractant gradients
into strongly localized intracellular responses. We show that the
capacity of a second messenger to establish and maintain localized
signals, is mainly determined by its dispersion range, 
= 
1)
with diffusion coefficients Dm in the range
of 0-5 µm2 s1 are most suitable.
Additional to short dispersion ranges, gradient sensing may include
positive feedback mechanisms that lead to local activation and global
inhibition of second-messenger production. To introduce the essential
nonlinear amplification, we have investigated models in which one or
more components of the signal transduction cascade translocate from the
cytosol to the second messenger in the plasma membrane. A one-component
model is able to amplify a 1.5-fold difference of receptor activity
over the cell length into a 15-fold difference of second-messenger
concentration. Amplification can be improved considerably by
introducing an additional activating component that translocates to the
membrane. In both models, communication between the front and the back
of the cell is mediated by partial depletion of cytosolic components,
which leads to both local activation and global inhibition. The results
suggest that a biochemically simple and general mechanism may explain
various signal localization phenomena not only in chemotactic cells but
also those occurring in morphogenesis and cell differentiation.
Biophys J, September 2001, p. 1314-1323, Vol. 81, No. 3
© 2001 by the Biophysical Society 0006-3495/01/09/1314/10 $2.00
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