Active transport of vesicles in neurons is modulated by mechanical tension

Abstract

Effective intracellular transport of proteins and organelles is critical in cells, and is especially important for ensuring proper neuron functionality. In neurons, most proteins are synthesized in the cell body and must be transported through thin structures over long distances where normal diffusion is insufficient. Neurons transport subcellular cargo along axons and neurites through a stochastic interplay of active and passive transport. Mechanical tension is critical in maintaining proper function in neurons, but its role in transport is not well understood. To this end, we investigate the active and passive transport of vesicles in Aplysia neurons while changing neurite tension via applied strain, and quantify the resulting dynamics. We found that tension in neurons modulates active transport of vesicles by increasing the probability of active motion, effective diffusivity, and induces a retrograde bias. We show that mechanical tension modulates active transport processes in neurons and that external forces can couple to internal (subcellular) forces and change the overall transport dynamics.

Segmentation of 3D Trajectories Acquired by TSUNAMI Microscope: An Application to EGFR Trafficking

“…In the complex intracellular environment, the active transport along microtubules has a values ranging from 1.4 to 2 (53). Whereas some biological studies also used the a value of 1.4 as a criterion for classification (54,55), an a value of 1.7 was used in a microfluidic experiment (36). In the same report, the criterion of Df % 0.1 was found suitable to achieve sufficient discrimination between active and passive motion (36).…”

“…In this study, we demonstrate an integrated trajectory analysis tool that adopts a combination of analytical strategies (34)(35)(36)(37)39) and classification parameters (MSD scaling exponent (53)(54)(55)(56), directional persistence (36,57), and confinement index (37,58)) in achieving effective segmentation and classification of both simulated and real-world trajectories. Our algorithm has achieved 81% accuracy in classifying segments along simulated 3D trajectories.…”

Active cell mechanics: Measurement and theory

“…In living cells it has been reported that force application fluidizes the cell mechanical properties [110] as measured by magnetic twisting cytometry. Direct measurement in living cells is sparse, however some studies have shown that applied deformation may also lead to decreased cytoplasmic resistance [111,112]. And metabolic activity was shown to fluidize the cytoplasm and facilitate motion of larger components in bacteria cells [113].…”

Modulating motility of intracellular vesicles in cortical neurons with nanomagnetic forces on-chip

“…1, 2 Today we know that mechanical forces or tension are involved in the formation of the cortical landscape folding, 3 in neuronal cell morphology, 4, 5 in neurite or axonal outgrowth, 6–10 in synaptic functioning, 1, 11 and in signal transduction 12, 13 through mechanically activated ion channels. 14, 15 A majority of these results are derived from in vitro experiments, where the mechanical stimulus was externally positioned.…”

“…14, 15 A majority of these results are derived from in vitro experiments, where the mechanical stimulus was externally positioned. Applying external forces through glass micropipettes, 5, 16, 17 magnetic/optical tweezers, 18–21 or stretchable cell platforms, 6, 11, 22 impart mechanical bending, compression, or expansion on the cell plasma membrane. Within this context it was reported that stretching axons resulted in faster accumulation of synaptic vesicles at the growth cone compared to un-stretched neurons.…”