Cytoskeletal Network Morphology Regulates Intracellular Transport Dynamics

Abstract

Intracellular transport is essential for maintaining proper cellular function in most eukaryotic cells, with perturbations in active transport resulting in several types of disease. Efficient delivery of critical cargos to specific locations is accomplished through a combination of passive diffusion and active transport by molecular motors that ballistically move along a network of cytoskeletal filaments. Although motor-based transport is known to be necessary to overcome cytoplasmic crowding and the limited range of diffusion within reasonable timescales, the topological features of the cytoskeletal network that regulate transport efficiency and robustness have not been established. Using a continuum diffusion model, we observed that the time required for cellular transport was minimized when the network was localized near the nucleus. In simulations that explicitly incorporated network spatial architectures, total filament mass was the primary driver of network transit times. However, filament traps that redirect cargo back to the nucleus caused large variations in network transport. Filament polarity was more important than filament orientation in reducing average transit times, and transport properties were optimized in networks with intermediate motor on and off rates. Our results provide important insights into the functional constraints on intracellular transport under which cells have evolved cytoskeletal structures, and have potential applications for enhancing reactions in biomimetic systems through rational transport network design.

Microtubules Regulate Spatial Localization and Availability of Insulin Granules in Pancreatic Beta Cells

“…ballistic) motor driven transport. That is, it is the topology of the MT network that influences cargo localization, not the specific motor dynamics (similar to (Ando et al, 2015)). Rather, the random granule motions observed in cells coupled with the structured nature of the network near the membrane is sufficient to generate directed motion of MT bound granules away from the membrane.…”

Hypothesis on interactions of macromolecules based on molecular vibration patterns in cells and tissues

“…These transport vehicles are established and composed in the Golgi apparatus. There are excellent reviews on the intracellular transport and their components (28)(29)(30)(31)(32)(33). Only very few aspects of these processes will be briefly delineated below:…”

The walkoff effect: cargo distribution implies motor type in bidirectional microtubule bundles

“…transport of neurotransmitters by kinesin in neurons), or where the MTs originate at the centrosome growing in the radial direction [52][53][54][55][56]. Transport along aligned networks [57], however it excluded bundled configurations. While the literature of the fundamental modeling of intracellular transport on networks is extensive, the authors are not aware of any work with goal of identifying distinct functions of each motor group on bi-directional bundled mobile MT networks.…”