Label-free visualization of cellular uptake and trafficking of nanoparticles by interferometric scattering microscopy

Interferometric scattering (iSCAT) microscopy is a new label-free optical imaging technique, recently developed to identify the nano-sized particles beyond a diffraction limit at a high temporal resolution. Here we report on the direct iSCAT visualization for the moment of cellular uptake of nanoparticles which are diffused in the plasma membrane of a live cell. After initial docking onto the plasma membrane, nanoparticles undergo abnormal sub-diffusion, characterized by simple Brownian motion, local confined diffusion, or Hopf diffusion in their long trajectories. During these processes, we sometimes observed that the scattering signals from nanoparticles in the plasma membrane are suddenly disappeared after exhibiting the oscillating motion in the vertical direction of a flat membrane. Such signal loss indicates that these nanoparticles escape from the focal plane of the microscope as they transport rapidly into the cytoplasmic area after cellular uptake. Our experimental results demonstrate that the label-free iSCAT microscopy can be used as a powerful tool to shed interferometric light on dynamic biophysical processes of various intracellular phenomena.