Cellular asymmetry and individuality in directional sensing

doi:10.1073/pnas.0601909103

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Cellular asymmetry and individuality in directional sensing

Azadeh Samadani, Jerome Mettetal, and Alexander van Oudenaarden^*

Department of Physics and G. R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139

Edited by Charles S. Peskin, New York University, New York, NY, and approved June 15, 2006

Received for publication March 9, 2006.

Abstract: It is generally assumed that single cells in an isogenic population,when exposed to identical environments, exhibit the same behavior.However, it is becoming increasingly clear that, even in a geneticallyidentical population, cellular behavior can vary significantlyamong cells. Here we explore this variability in the gradient-sensingresponse of Dictyostelium cells when exposed to repeated spatiotemporalpulses of chemoattractant. Our experiments show the responseof a single cell to be highly reproducible from pulse to pulse.In contrast, a large variability in the response direction andmagnitude is observed from cell to cell, even when differentcells are exposed to the same pulse. First, these results indicatethat the gradient-sensing network has inherent asymmetries thatcan significantly impact the ability of cells to faithfullysense the direction of extracellular signals (cellular asymmetry).Second, we find that the magnitude of this asymmetry variesgreatly among cells. Some cells are able to accurately followthe direction of an extracellular stimulus, whereas, in othercells, the intracellular asymmetry dominates, resulting in apolarization axis that is independent of the direction of theextracellular cue (cellular individuality). We integrate theseexperimental findings into a model that treats the effectivesignal a cell detects as the product of the extracellular signaland the asymmetric intracellular signal. With this model wesuccessfully predict the population response. This cellularindividuality and asymmetry might fundamentally limit the fidelityof signal detection; in contrast, however, it might be beneficialby diversifying phenotypes in isogenic populations.

Key Words: modeling • stochastic • Dictyostelium • chemotaxis • variability

Author contributions: A.S., J.M., and A.v.O. designed research;A.S. and J.M. performed research; A.S., J.M., and A.v.O. analyzeddata; and A.S., J.M., and A.v.O. wrote the paper.

Conflict of interest statement: No conflicts declared.

This paper was submitted directly (Track II) to the PNAS office.

*To whom correspondence should be addressed. E-mail: avano{at}mit.edu