  Supported lipid bilayers have been studied intensively over the past two
decades. In this work, we study the diffusion of single gold nanoparticles
(GNPs) with diameter of 20 nm attached to GM1 ganglioside or DOPE lipids at
different concentrations in supported DOPC bilayers. The indefinite
photostability of GNPs combined with the high sensitivity of interferometric
scattering microscopy (iSCAT) allows us to achieve 1.9 nm spatial precision at
1 ms temporal resolution, while maintaining long recording times. Our
trajectories visualize strong transient confinements within domains as small as
20 nm, and the statistical analysis of the data reveals multiple mobilities and
deviations from normal diffusion. We present a detailed analysis of our
findings and provide interpretations regarding the effect of the supporting
substrate and GM1 clustering. We also comment on the use of high-speed iSCAT
for investigating diffusion of lipids, proteins or viruses in lipid membranes
with unprecedented spatial and temporal resolution.
