The role of the cytoskeleton in volume regulation and beading transitions in PC12 neurites

We present investigations on volume regulation and beading shape transitions in PC12 neurites conducted using a flow-chamber technique. By disrupting the cell cytoskeleton with specific drugs we investigate the role of its individual components in the volume regulation response. We find that microtubule disruption increases both swelling rate and maximum volume attained, but does not affect the ability of the neurite to recover its initial volume. In addition, investigation of axonal beading –also known as pearling instability– provides additional clues on the mechanical state of the neurite. We conclude that the initial swelling phase is mechanically slowed down by microtubules, while the volume recovery is driven by passive diffusion of osmolites. Our experiments provide a framework to investigate the role of cytoskeletal mechanics in volume homeostasis.