Single particle algorithms to reveal cellular nanodomain organization

Abstract: Formation, maintenance and physiology of high-density protein-enriched organized nanodomains, first observed in electron microscopy images, remains challenging to investigate due to their small sizes. However, these regions regulate molecular trafficking, assembly and sorting required for higher cell functions, such as communication or plastic changes. Over the past ten years, super-resolution single-particle trajectories (SPTs) have been used to sample these sub-cellular environments at a nanometer resolution for both membrane and soluble proteins. We present here data analysis developments and algorithms that convert high-throughput molecular trajectories into maps of molecular density, diffusion and local drift organization. These approaches transform intrinsic trajectory properties into statistics of the underlying cellular organization. The automatic identification of large numbers of high-density regions allows quantifying their boundary location and organization, their stability over time and their ability to transiently retain molecules. To conclude recent automated algorithms can now be used to extract biophysical parameters of sub-cellular nanodomains over a large amount of trajectories.