Abstract
Intracellular transport is pivotal for cell growth and survival. Malfunctions in this process have been associated with devastating neurodegenerative diseases, highlighting the need for a deeper understanding of the mechanisms involved. Here, we use an experimental methodology that leads neurites of differentiated PC12 cells into either one of two configurations: a one-dimensional configuration, where the neurites align along lines, or a two-dimensional configuration, where the neurites adopt a random orientation and shape on a flat substrate. We subsequently monitored the motion of functional organelles, the lysosomes, inside the neurites. Implementing a time-resolved analysis of the mean-squared displacement, we quantitatively characterized distinct motion modes of the lysosomes. Our results indicate that neurite alignment gives rise to faster diffusive and super-diffusive lysosomal motion than the situation in which the neurites are randomly oriented. After inducing lysosome swelling through an osmotic challenge by sucrose, we confirmed the predicted slowdown in diffusive mobility. Surprisingly, we found that the swelling-induced mobility change affected each of the (sub-/super-)diffusive motion modes differently and depended on the alignment configuration of the neurites. Our findings imply that intracellular transport is significantly and robustly dependent on cell morphology, which might in part be controlled by the extracellular matrix.
Highlights
One critical function— for the growth and maintenance of homeostasis and for the survival of a cell—is the transport of proteins, molecules, organelles and debris to specific locations within the cell
We investigated the motion of lysosomes inside neurites of differentiated PC12 cells, when those adopt a random orientation on the two-dimensional culture surface, versus when they are prompted to adhere to a onedimensional configuration by means of chemical surface patterning
Microscale plasma-initiated patterning of laminin guides the neurites of differentiated PC12 cells along 2-μm-wide lines
Summary
One critical function— for the growth and maintenance of homeostasis and for the survival of a cell—is the transport of proteins, molecules, organelles and debris to specific locations within the cell. This allocation is of tremendous significance, especially for neuronal cells owing to the extreme size of their axons; for instance, axons of human motor neurons can reach a length of 1 m, starting from the brain and extending as far as the end of the spine. Intracellular distribution of molecules and organelles is achieved mainly via two mechanisms: passive diffusion and active, motor-driven transport along microtubules and actin filaments [8]. In order to characterize intracellular dynamics and extract values such as the velocity of the motor-mediated transport or the diffusion coefficient of passive motion, several models have been implemented [13,14,15]
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