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Abstract
Intracellular transport is vital for the proper functioning and survival of a cell. Cargo (proteins, vesicles, organelles, etc) is transferred from its place of creation to its target locations via molecular motor assisted transport along cytoskeletal filaments. The transport efficiency is strongly affected by the spatial organization of the cytoskeleton, which constitutes an inhomogeneous, complex network. In cells with a centrosome microtubules grow radially from the central microtubule organizing center towards the cell periphery whereas actin filaments form a dense meshwork, the actin cortex, underneath the cell membrane with a broad range of orientations. The emerging ballistic motion along filaments is frequently interrupted due to constricting intersection nodes or cycles of detachment and reattachment processes in the crowded cytoplasm. In order to investigate the efficiency of search strategies established by the cell’s specific spatial organization of the cytoskeleton we formulate a random velocity model with intermittent arrest states. With extensive computer simulations we analyze the dependence of the mean first passage times for narrow escape problems on the structural characteristics of the cytoskeleton, the motor properties and the fraction of time spent in each state. We find that an inhomogeneous architecture with a small width of the actin cortex constitutes an efficient intracellular search strategy.
Highlights
The accurate delivery of various cargoes is of great importance for maintaining the correct function of cells and organisms
We perform extensive Monte Carlo simulations in order to analyze the dependence of the search efficiency to narrow escapes alongside a cell’s membrane on the spatial organization of the cytoskeleton as well as the motor performance at network intersections
For that purpose we define the mean first passage time (MFPT) to a target as the ensemble average over first passage events of 5 ́ 105 independent realizations of the walk, in which all cargoes are initially located at the center of the cell and start moving in an uniformly distributed direction Q Î [-p; p)
Summary
The accurate delivery of various cargoes is of great importance for maintaining the correct function of cells and organisms. Particles, such as vesicles, proteins, organelles, have to be transported to their specific destinations. In order to enable this cargo transfer, cells are equipped with a complex filament network and specialized motor proteins. The cytoskeleton serves as tracks for molecular motors. They convert the energy provided by adenosine triphosphate hydrolysis into active motion along the cytoskeletal filaments, while they simultaneously bind to cargo [1, 2]. In addition to intracellular transport, the dynamic cytoskeleton and its associated motors stabilize the cell shape, adjust it to different environmental circumstances, and drive cell motility or division [3]
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