Spatial cytoskeleton organization supports targeted intracellular transport

TL;DR

This paper models how the spatial organization of the cytoskeleton enhances targeted intracellular transport efficiency by analyzing random velocity models with intermittent arrest states for different cellular transport tasks.

Contribution

It introduces a novel random velocity model with intermittent arrest states to evaluate the efficiency of cytoskeleton-guided intracellular transport strategies.

Findings

Cells optimize transport efficiency with a narrow actin cortex.

Spatial organization improves search strategies for cargo delivery.

Model predicts reduced mean first passage times with organized cytoskeleton.

Abstract

The efficiency of intracellular cargo transport from specific source 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 realizes a spatially inhomogeneous intermittent search strategy. In order 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: i) the narrow escape problem, which emerges during cargo transport to a synapse or other specific region of the cell membrane, ii) the reaction problem, which considers the binding time of two particles within the cell, and iii) 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.