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

Journal Article · · Journal of Chemical Physics
DOI:https://doi.org/10.1063/1.4901888· OSTI ID:22413255
;  [1];  [1]
  1. FOM Institute AMOLF, Science Park 104, 1098 XG Amsterdam (Netherlands)

Clustering of molecules on biological membranes is a widely observed phenomenon. A key example is the clustering of the oncoprotein Ras, which is known to be important for signal transduction in mammalian cells. Yet, the mechanism by which Ras clusters form and are maintained 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.

OSTI ID:
22413255
Journal Information:
Journal of Chemical Physics, Vol. 141, Issue 20; Other Information: (c) 2014 AIP Publishing LLC; Country of input: International Atomic Energy Agency (IAEA); ISSN 0021-9606
Country of Publication:
United States
Language:
English