title: Heterogeneity of AMPA receptor trafficking and molecular interactions revealed by superresolution analysis of live cell imaging.
abstract: Simultaneous tracking of many thousands of individual particles in live cells is possible now with the advent of high-density superresolution imaging methods. We present an approach to extract local biophysical properties of cell-particle interaction from such newly acquired large collection of data. Because classical methods do not keep the spatial localization of individual trajectories, it is not possible to access localized biophysical parameters. In contrast, by combining the high-density superresolution imaging data with the present analysis, we determine the local properties of protein dynamics. We specifically focus on AMPA receptor (AMPAR) trafficking and estimate the strength of their molecular interaction at the subdiffraction level in hippocampal dendrites. These interactions correspond to attracting potential wells of large size, showing that the high density of AMPARs is generated by physical interactions with an ensemble of cooperative membrane surface binding sites, rather than molecular crowding or aggregation, which is the case for the membrane viral glycoprotein VSVG. We further show that AMPARs can either be pushed in or out of dendritic spines. Finally, we characterize the recurrent step of influenza trajectories. To conclude, the present analysis allows the identification of the molecular organization responsible for the heterogeneities of random trajectories in cells.
authors.affiliation: Group of Computational Biology and Applied Mathematics, Institute of Biology, Ecole Normale Supérieure, 46 Rue d'Ulm, 75005 Paris, France.
authors.forename: Nathanael
authors.initials: N
authors.lastname: Hoze
authors.forename: Deepak
authors.initials: D
authors.lastname: Nair
authors.forename: Eric
authors.initials: E
authors.lastname: Hosy
authors.forename: Christian
authors.initials: C
authors.lastname: Sieben
authors.forename: Suliana
authors.initials: S
authors.lastname: Manley
authors.forename: Andreas
authors.initials: A
authors.lastname: Herrmann
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Sibarita
authors.forename: Daniel
authors.initials: D
authors.lastname: Choquet
authors.forename: David
authors.initials: D
authors.lastname: Holcman
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena; D003712:Dendrites / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology*; D008853:Microscopy / Q000379:methods*; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*
chemical_list: D018091:Receptors, AMPA