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Positive feedback regulation is ubiquitous in cell signaling networks, oftenleading to binary outcomes in response to graded stimuli. However, the role ofsuch feedbacks in clustering, and in spatial spreading of activated molecules,has come to be appreciated only recently. We focus on the latter, using asimple model developed in the context of Ras activation with competing negativeand positive feedback mechanisms. We find that positive feedback, in thepresence of slow diffusion, results in clustering of activated molecules on theplasma membrane, and rapid spatial spreading as the front of the clusterpropagates with a constant velocity (dependent on the feedback strength). Theadvancing fronts of the clusters of the activated species are rough, withscaling consistent with the Kardar-Parisi-Zhang (KPZ) equation in onedimension. Our minimal model is general enough to describe signal transductionin a wide variety of biological networks where activity in themembrane-proximal region is subject to feedback regulation.

Positive Feedback Regulation Results in Spatial Clustering and Fast Spreading of Active Signaling Molecules on a Cell Membrane