Impact of neurite alignment on organelle motion.

Abstract

Intracellular transport is pivotal for cell growth and survival. Malfunctions in this process have been associated with devastating neurodegenerative diseases, posing a need for deeper understanding of the involved mechanisms. Here, we used an experimental methodology that lead neurites of differentiated PC12 cells in either of two configurations: an one-dimensional, where the neurites align along lines, or a two-dimensional configuration, where the neurites adopt a random orientation and shape on a fiat 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 in comparison to the situation where 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 be in part controlled by the extracellular matrix.