title: Positive feedback can lead to dynamic nanometer-scale clustering on cell membranes.
abstract: 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.
authors.affiliation: FOM Institute AMOLF, Science Park 104, 1098 XG Amsterdam, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Wehrens
authors.affiliation: FOM Institute AMOLF, Science Park 104, 1098 XG Amsterdam, The Netherlands.
authors.forename: Pieter Rein
authors.initials: PR
authors.lastname: ten Wolde
authors.affiliation: FOM Institute AMOLF, Science Park 104, 1098 XG Amsterdam, The Netherlands.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mugler
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry*; D006801:Humans; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry*; D018631:ras Proteins / Q000378:metabolism
chemical_list: D018631:ras Proteins