Mapping the Energy Landscapes of the Glycine Receptor in the Post-Synaptic Neuronal Membrane

The movement of proteins in the cell membrane is governed by the local friction and their interactions with molecular partners. Yet, most experimental descriptions fail to unequivocally distinguish these effects; instead, they combine the diffusive and energetic contributions into an effective diffusion coefficient or anomalous exponent. Here, we show how the diffusion and energy landscapes of membrane proteins can be mapped separately over the entire cell surface using high-density single-molecule imaging and statistical inference [1]. In the case of glycine neuroreceptors, we demonstrate that scaffolds at inhibitory synapses act as energy traps with a depth modulated by the properties of the intracellular loop that mediates the receptor-scaffold interactions. Furthermore, we bridge the gap between local properties of the membrane environment and characteristics of the mobility at the cellular scale by simulating random walks in the inferred maps and computing estimators such as the propagator, mean square displacement, and first-passage time. Results are used to investigate the relation between numbers of receptors and synaptic plasticity. Overall, our approach provides a versatile framework with which to analyze biochemical interactions in situ.[1] J.-B Masson et al, Nat. Chem. (submitted)View Large Image | View Hi-Res Image | Download PowerPoint Slide