Passive diffusion accounts for the majority of intracellular vesicle 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 µm 2 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 are involved in constitutive secretion 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.