title: Intracellular transport of insulin granules is a subordinated random walk.
abstract: 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.
authors.affiliation: James Franck Institute, University of Chicago, Chicago, IL 60637, USA.
authors.forename: S M Ali
authors.initials: SM
authors.lastname: Tabei
authors.forename: Stanislav
authors.initials: S
authors.lastname: Burov
authors.forename: Hee Y
authors.initials: HY
authors.lastname: Kim
authors.forename: Andrey
authors.initials: A
authors.lastname: Kuznetsov
authors.forename: Toan
authors.initials: T
authors.lastname: Huynh
authors.forename: Justin
authors.initials: J
authors.lastname: Jureller
authors.forename: Louis H
authors.initials: LH
authors.lastname: Philipson
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Dinner
authors.forename: Norbert F
authors.initials: NF
authors.lastname: Scherer
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D022142:Secretory Vesicles / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology
chemical_list: D007328:Insulin; D050257:Tubulin Modulators; D014747:Vinblastine