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.
Highlights
Intracellular transport of various cargoes from specific origins to target locations is crucial for the correct function of cells and organisms
In contrast to [49,50], we systematically study the impact of pausing states on the efficiency of intracellular transport task
For large exit zones aexitz2p, the searcher is likely to find the escape by first encounter with the membrane; the initial location of the searcher has a strong influence on the mean first passage time (MFPT)
Summary
Intracellular transport of various cargoes from specific origins to target locations is crucial for the correct function of cells and organisms. The cytoskeleton is a self-organizing filamentous network that shapes the mechanical and rheological characteristics of the cell [1,2,3,4,5], drives cell motility or division [6], and coordinates cargo transport between different cellular regions [7,8,9]. The main components of the cytoskeleton that are involved in intracellular transport are the polarized microtubules and actin filaments. Associated motor proteins walk actively along these filaments as they simultaneously bind to cargo particles [10,11]. Correct cargo delivery depends on the coordination of microtubule- and actin-based transport. A prominent example is the transfer of pigment granules between the actin and the microtubule network of melanophores, which is tightly controlled by the intracellular level of cyclic adenosine monophosphate [20]
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