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Michael J Saxton

Publications and source records attributed to Michael J Saxton.

3 recordsLinked to original sources

A biological interpretation of transient anomalous subdiffusion. I. Qualitative model.

Anomalous subdiffusion has been reported for two-dimensional diffusion in the plasma membrane and three-dimensional diffusion in the nucleus and cytoplasm. If a particle diffuses in a suitable infinite hierarchy of binding sites, diffusion is well known to be anomalous at all times. But if the hierarchy is finite, diffusion is anomalous at short times and normal at long times. For a prescribed set of binding sites, Monte Carlo calculations yield the anomalous diffusion exponent and the average time over which diffusion is anomalous. If even a single binding site is present, there is a very short, almost artifactual, period of anomalous subdiffusion, but a hierarchy of binding sites extends the anomalous regime considerably. As is well known, an essential requirement for anomalous subdiffusion due to binding is that the diffusing particle cannot be in thermal equilibrium with the binding sites; an equilibrated particle diffuses normally at all times. Anomalous subdiffusion due to barriers, however, still occurs at thermal equilibrium, and anomalous subdiffusion due to a combination of binding sites and barriers is reduced but not eliminated on equilibration. This physical model is translated directly into a plausible biological model testable by single-particle tracking.

Binding Sites↗

Unexpected mobility variation among individual secretory vesicles produces an apparent refractory neuropeptide pool.

Most stored neuropeptide cannot be released from nerve terminals suggesting the existence of a refractory pool of dense core vesicles (DCVs). Past fluorescence photobleaching recovery, single particle tracking and release experiments suggested that the refractory neuropeptide pool corresponds to a distinct immobile fraction of cytoplasmic DCVs. However, tracking of hundreds of individual green fluorescent protein-labeled neuropeptidergic vesicles by wide-field or evanescent-wave microscopy shows that a separate immobile fraction is not evident. Instead, the DCV diffusion coefficient (D) distribution is unusually broad and asymmetric. Furthermore, the distribution shifts with a release facilitator. This unexpected variation, which could reflect heterogeneity among vesicles or in their medium, is shown to generate the appearance of a regulated refractory neuropeptide pool.

Animals↗