Run, Wander, and Drift: Multi-modal Transport in the Eukaryotic Cytoplasm

Abstract

Eukaryotic cells utilize a variety of mechanisms to transport particles of different sizes throughout the cytoplasm. Commonly employed transport modes include diffusion driven by stochastic fluctuations in the medium, processive motor-driven transport along cytoskeletal tracks, and advection in a flowing cytoplasmic fluid. We use analytical theory and simulations, grounded in the physics of stochastic processes and fluid dynamics and coupled with analysis of in vivo data on organelle motion, to explore the efficiency and relative contributions of these different modes of transport. Using several example cellular systems, we identify both the physical limits and synergistic nature of multi-modal transport, where individual organelles switch between active and passive regimes. In particular, we highlight the potential importance of hydrodynamic entrainment and large-scale cytoplasmic flow associated with cell deformation to the dispersion of vesicles within fungal hyphae and motile leukocytes, respectively. Peroxisome transport in hyphae is shown to lie in a regime where both passive diffusion and directed “hitch-hiking” runs contribute substantially to the organelles' ability to efficiently find intracellular targets. We also show that spatial localization of neuronal mitochdria by glucose-dependent regulation of transport is sensitive to intracellular glucose levels in a manner dependent on the balance of mitochondrial transport modes. These results highlight the importance of combining together a variety of passive and active transport mechanisms to efficiently distribute, deliver, and organize organelles within eukaryotic cells.