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Interferometric scattering microscopy reveals microsecond nanoscopic protein motion on a live cell membrane

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Taylor,  Richard W.
Sandoghdar Division, Max Planck Institute for the Science of Light, Max Planck Society;

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Gholami Mahmoodabadi,  Reza
Sandoghdar Division, Max Planck Institute for the Science of Light, Max Planck Society;

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Schambony,  Alexandra
Sandoghdar Division, Max Planck Institute for the Science of Light, Max Planck Society;
external;

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Sandoghdar,  Vahid
Sandoghdar Division, Max Planck Institute for the Science of Light, Max Planck Society;
Sandoghdar Division, Max-Planck-Zentrum für Physik und Medizin, Max Planck Institute for the Science of Light, Max Planck Society;

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Citation

Taylor, R. W., Gholami Mahmoodabadi, R., Rauschenberger, V., Giessl, A., Schambony, A., & Sandoghdar, V. (2019). Interferometric scattering microscopy reveals microsecond nanoscopic protein motion on a live cell membrane. Nature Photonics, 13, 480-487. doi:10.1038/s41566-019-0414-6.


Cite as: https://hdl.handle.net/21.11116/0000-0002-B9EB-5
Abstract
Much of the biological functions of a cell are dictated by the intricate motion of proteins within its membrane over a spatial range of nanometers to tens of micrometers and time intervals of microseconds to minutes. While this rich parameter space is not accessible to fluorescence microscopy, it can be within reach of interferometric scattering (iSCAT) particle tracking. Being sensitive even to single unlabeled proteins, however, iSCAT is easily accompanied by a large speckle-like background, which poses a substantial challenge for its application to cellular imaging. Here, we show that these difficulties can be overcome and demonstrate tracking of transmembrane epidermal growth factor receptors (EGFR) with nanometer precision in all three dimensions at up to microsecond speeds and tens of minutes duration. We provide unprecedented examples of nanoscale motion and confinement in ubiquitous processes such as diffusion in the plasma membrane, transport on filopodia, and endocytosis.