Vesicular diffusion and thermal forces

The concept that an endothelial vesicular shuttle serves much if not all the function of the large pores of the microcirculation for macromolecular transport has been current for 2 decades. Morphologists have expended much ingenuity in the study of plasmalemmal vesicles by the use of nonenzymatic and enzymatic tracers combined with electron microscopy. Several theoretical models of vesicular transport have been suggested, all of which assume vesicular migration by Brownian or thermal motion. Two such models based on simple diffusion are described, and more recent models in which vesicular diffusion is constrained by long-range hydrodynamic interaction with the plasmalemma are discussed. Theoretical models agree in predicting a vesicular transport time of the order of seconds. Only recently has experimental evidence appeared that tends to corroborate such predictions. Reports that frog mesenteric capillary endothelium fixed with formaldehyde-glutaraldehyde contains very few (approximately 1%) free vesicles are at variance with many in vivo tracer studies and inconsistent with the shuttle theory. It is possible that aldehyde fixation gives a poor representation of the state of the endothelium in vivo. It would seem that more instantaneous methods of fixation, such as rapid freezing, combined with tracer studies and serial sectioning, may be required to resolve this contradiction.