Intracellular transport of insulin granules is a subordinated random walk

We quantitatively analyzed particle tracking data on insulin granules expressing fluorescent fusion proteins in MIN6 cells to better understand the motions contributing to intracellular transport and, more generally, the means for characterizing systems far from equilibrium. Care was taken to ensure...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2013-03, Vol.110 (13), p.4911-4916
Main Authors: Tabei, S. M. Ali, Burov, Stanislav, Kim, Hee Y., Kuznetsov, Andrey, Huynh, Toan, Jureller, Justin, Philipson, Louis H., Dinner, Aaron R., Scherer, Norbert F.
Format: Article
Language:English
Subjects:
Animals
Biological Transport, Active - drug effects
Biological Transport, Active - physiology
Cell Line
Cells
Correlation analysis
Ergodic theory
Exocytosis
Insulin
Insulin - metabolism
Measurement
Mice
Microtubules
Microtubules - metabolism
Models, Biological
Particle tracks
Particle trajectories
Physical Sciences
Proteins
Quantum statistics
Random walk
Secretion
Secretory Vesicles - metabolism
Trajectories
Tubulin Modulators - pharmacology
Vinblastine - pharmacology
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Summary:We quantitatively analyzed particle tracking data on insulin granules expressing fluorescent fusion proteins in MIN6 cells to better understand the motions contributing to intracellular transport and, more generally, the means for characterizing systems far from equilibrium. Care was taken to ensure that the statistics reflected intrinsic features of the individual granules rather than details of the measurement and overall cell state. We find anomalous diffusion. Interpreting such data conventionally requires assuming that a process is either ergodic with particles working against fluctuating obstacles (fractional Brownian motion) or nonergodic with a broad distribution of dwell times for traps (continuous-time random walk). However, we find that statistical tests based on these two models give conflicting results. We resolve this issue by introducing a subordinated scheme in which particles in cages with random dwell times undergo correlated motions owing to interactions with a fluctuating environment. We relate this picture to the underlying microtubule structure by imaging in the presence of vinblastine. Our results provide a simple physical picture for how diverse pools of insulin granules and, in turn, biphasic secretion could arise.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1221962110