Section: New Results

The impact of anomalous diffusion on cell signaling

This year, we published two papers describing the impact of diffusion and clustering in membrane domains for ubiquitous biological pathways. In the first paper [18] , we showed that clustering of receptors in membrane domains affect severely the activation of 'hit and run' type of pathways (eg. IRS1, G proteins). This is a pure diffusion result and it is obtained without modifying molecular affinity. This impairment is dramatically important when receptors are highly clustered such are the cases for insulin and adrenergic receptors. In the same direction, we studied the impact of modified diffusion on the other ubiquitous pathway: enzyme/substrate equilibrium [10] . In that case diffusion was modified either using subdiffusion - obstacles and Continuous Time Random Walk - or using space-based inhomogeneous diffusion. We showed that while impairing diffusion all three mechanisms behave differently in the stationary regime. Therefore it it not possible to assume simple space-dependent diffusion for subdiffusion at the equilibrium limit (as it is always assumed). Furthermore, we showed that in the case of space-dependent diffusion - the shape of the diffusion profile can drastically affect the equilibrium and modify the pathway. Since these three phenomenons are thought to occur either in the membrane or the cytosplasm, our results show they can have non trivial effect of all chemical reaction occurring within these medium.

This research will be carried on in the group in 2014 and expanded by the more mathematical approaches initiated in 2013 by collaborations with V Calvez (Numed Inria Lyon), T Lepoutre (Dracula, INIA Lyon) and S. Fedotov (Univ Manchester, UK).