Spatial Cytoskeleton Organization Supports Targeted Intracellular Transport

Abstract

The efficiency of intracellular cargo transport from specific sources to target locations is strongly dependent upon molecular motor-assisted motion along the cytoskeleton. Radial transport along microtubules and lateral transport along the filaments of the actin cortex underneath the cell membrane are characteristic for cells with a centrosome. The interplay between the specific cytoskeleton organization and the motor performance results in a spatially inhomogeneous intermittent search strategy. To analyze the efficiency of such intracellular search strategies, we formulate a random velocity model with intermittent arrest states. We evaluate efficiency in terms of mean first passage times for three different, frequently encountered intracellular transport tasks: 1) the narrow escape problem, which emerges during cargo transport to a synapse or other specific region of the cell membrane; 2) the reaction problem, which considers the binding time of two particles within the cell; and 3) the reaction-escape problem, which arises when cargo must be released at a synapse only after pairing with another particle. Our results indicate that cells are able to realize efficient search strategies for various intracellular transport tasks economically through a spatial cytoskeleton organization that involves only a narrow actin cortex rather than a cell body filled with randomly oriented actin filaments.

Are Synapse-Like Structures a Possible Way for Crosstalk of Cancer with Its Microenvironment?

“…The cytoskeleton is remodeled, the Golgi apparatus, and the microtubule-organizing center (MTOC) move to the IS formation region [48,49]. All these rearrangements facilitate and allow the directed secretion within the synapse [49][50][51][52]. Activation/inhibition of T cells requires three signals.…”

“…The location of the centrosome is also drastically changed upon recognition of the target cell. The centrosome moves from the back-end of the cell to its front edge where a synapse forms [48][49][50][51][52]. The involvement of the cytoskeleton in cluster formation has been shown schematically in Figure 2.…”

Full distribution of first exit times in the narrow escape problem

“…Despite of this considerable body of works published on the NEP, information beyond the mean FRT is scarce, only two recent analytical and numerical works consider the full distributions of first-passage times to perfect targets and only in two-dimensional settings [33,34]. In fact, the NEP typically involves a broad spectrum of time scales giving rise to a rich and interesting structure of the probability density function (PDF) of FRTs with different time regimes.…”

The narrow escape problem in a circular domain with radial piecewise constant diffusivity

“…Those particle are impeded by the central obstacle to move quickly towards the target, they remain jammed for a longer time when the obstacle is large. Thus the MFPT for particles starting close to the escape region increases with increasing ∆, whereas the MFPT of particles starting far away from 11), is plotted as a function of δ = ∆/R and compared to its analytical expression (24). This function goes to 1/8π for ∆ → R and diverges as πR/6∆ for ∆ → 0.…”

“…Recently the narrow escape problem was studied in spatially inhomogeneous environments [8]. The type of spatial inhomogeneity was inspired by the spatial organization of the cytoskeleton of cells with a centrosome [9,23,24] along which ballistic transport is possible in addition to simple diffusion: a circular or spherical domain is divided into two concentric shells, the inner shell allowing only radial ballistic transport (and diffusion) and the outer shell of width ∆ allows multi-directional ballistic transport (and diffusion). In these studies it was shown that the MFPT for the narrow escape problem is optimizable with respect to the width of the outer shell.…”