Positive feedback can lead to dynamic nanometer-scale clustering on cell membranes

Clustering of molecules on biological membranes is a widely observed phenomenon. In some cases, such as the clustering of Ras proteins on the membranes of mammalian cells, proper cell signaling is critically dependent on the maintenance of these clusters. Yet, the mechanism by which clusters form and are maintained in these systems remains unclear. Recently, it has been discovered that activated Ras promotes further Ras activation. Here we show using particle-based simulation that this positive feedback is sufficient to produce persistent clusters of active Ras molecules at the nanometer scale via a dynamic nucleation mechanism. Furthermore, we find that our cluster statistics are consistent with experimental observations of the Ras system. Interestingly, we show that our model does not support a Turing regime of macroscopic reaction-diffusion patterning, and therefore that the clustering we observe is a purely stochastic effect, arising from the coupling of positive feedback with the discrete nature of individual molecules. These results underscore the importance of stochastic and dynamic properties of reaction diffusion systems for biological behavior.

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