Wanted: Scalable Tracers for Diffusion Measurements

We review candidate species for two-dimensional diffusion in membranes and threedimensional diffusion in the cytoplasm and nucleus, briefly in the text and in detail in the Supporting Information

Michael J. Saxton


Scholarcy highlights

  • Scalable tracers are potentially a useful tool to examine diffusion mechanisms and to predict diffusion coefficients, for hindered diffusion in complex, heterogeneous, or crowded systems
  • We consider two cases: tracers scalable in size and tracers scalable in deformability. These tracers are called “scalable” rather than “homologous” to emphasize that we need chemical homology and constant dynamics and to emphasize that the series of tracers is explicitly designed so that one property can be varied while the others are held as constant as possible
  • Tracers scalable in size are defined as a homologous series of tracers varying in size but with constant shape; constant structure, implying in particular that branching must not vary with size; constant surface chemistry so a constant interaction with the environment, both attractive and repulsive, and a constant solvation shell; constant deformability; constant dynamics, that is, no change in the diffusion mechanism with size, in particular no transition between ordinary diffusion and reptation
  • Polydispersity ought to be an explicit variable, not just whatever the manufacturer, synthesis, or microorganism supplies; metabolically inert, not metabolized by the cell, not modified by the cell, not affecting metabolism except as inert crowders, and not bound in mobile complexes or to the cytoskeleton; continuously variable in radius, though tracers must be made out of atoms; with tunable surface properties; with a low tendency to associate or crystallize; made by a scalable synthesis in which the size can be readily controlled by varying concentrations, reaction times, surfactants, or other reaction conditions; and available in a wide range of sizes, covering the entire range of length scales needed for a cell or other complex fluid
  • Especially measurements of hindered diffusion, would be improved if two types of measurements were made and clearly distinguished: scalable tracers to test the effect of size alone and nonscalable tracers at fixed size to test the effect of shape, structure, surface chemistry, deformability, and diffusion mechanism
  • The emphasis here has been on approximately spherical tracers for diffusion measurements in 3D complex fluids
  • The ideal experiment would compare random coil to spherical proteins using a series of proteins varying in disulfide crosslinking

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