Passive diffusion accounts for the majority of intracellular nanovesicle transport

During membrane trafficking, a vesicle formed at the donor compartment must travel to the acceptor membrane before fusing. For large carriers, it is established that this transport is motor-driven; however, the mode by which small vesicles, which outnumber larger carriers, are transported is poorly characterized. Here, we show that intracellular nanovesicles (INVs), a substantial class of small vesicles, are highly mobile within cells and that this mobility depends almost entirely on passive diffusion (0.1-0.3 μm² s^-1). Using single particle tracking, we describe how other small trafficking vesicles have a similar diffusive mode of transport that contrasts with the motor-dependent movement of larger endolysosomal carriers. We also demonstrate that a subset of INVs is involved in exocytosis and that delivery of cargo to the plasma membrane during exocytosis is decreased when diffusion of INVs is specifically restricted. Our results suggest that passive diffusion is sufficient to explain the majority of small vesicle transport.