Wanted: Scalable Tracers for Diffusion

Abstract

Scalable tracers are potentially a useful tool to understand diffusion mechanisms and to predict diffusion coefficents, particularly for hindered diffusion in complex, heterogeneous, or crowded systems. Scalable tracers are defined as a homologous series of tracers varying in size but with the same shape, structure, surface chemistry, flexibility, and diffusion mechanism. Both chemical homology and constant dynamics are required. Specifically, branching must not vary with size, and there must be no transition between ordinary diffusion and reptation. Ideally the tracers would be uniform, monodisperse, metabolically inert cylinders in 2D or spheres in 3D with continuously variable radius and tunable surface properties. Scalable tracers would facilitate more rigorous diffusion measurements in which two types of measurements would be clearly distinguished: using scalable tracers to find the mean diffusion coefficient as a function of size, and using nonscalable tracers to find the variation due to differences in shape, surface properties, and the like. Candidate scalable tracers are discussed for 2D diffusion in membranes and 3D diffusion in cytoplasm and nucleoplasm. Specific recommendations for 3D measurements include the use of synthetic dendrimers or random hyperbranched polymers instead of dextran, and the use of core-shell quantum dots in which the shell thickness is used to vary the overall diameter. A set of scalable tracers varying in flexibility would also be useful. These would be made by varying the density of crosslinking in a polymer, to make say “reinforced Ficoll” or “reinforced hyperbranched polyglycerol.” (Supported by NIH grant GM038133.)