Slowed diffusion of single nanoparticles in the extracellular microenvironment of living cells revealed by darkfield microscopy.

We obtained vertical distribution of diffusion coefficients of single gold nanoparticles (AuNPs) in the extracellular solution space of living cells with optical sectioning darkfield microscopy. It was identified that before reaching the plasma membrane surface during their cellular uptake process, AuNPs must diffuse through a viscous pericellular "buffer zone" several microns thick where their motion is retarded significantly. The pericellular layer exists in two different cell types and is unrelated to the surface chemistry of AuNPs. Further studies on its properties and manipulation may help the development of nanoparticle probes and carriers.