Transport, Delivery, and Kinetics in Tubular Organelle Networks*

The endoplasmic reticulum (ER) forms an interconnected tubular network that plays a crucial role in cell functions ranging from protein quality control to calcium signalling. These functions require proteins to move within the networked architecture in order to find their binding partners. We leverage physical modeling, combined with analysis of live-cell imaging data, to investigate the transport of particles confined within a tubular network. We have developed new methods for efficient numerical simulations of diffusive network transport, for exact calculations of mean first passage times, and for analysis of dynamic experimental data such as single particle trajectories and spreading of photoactivated probes.

Our work highlights the importance of network connectivity in speeding diffusion-limited kinetics. Furthermore, we establish that broadly dispersed targets over a network can enhance search rates, providing the first functional explanation for the prevalence of peripheral ER exit sites. Finally, we discuss the limitations imposed by diffusive transport on ER functions such as localized calcium release, implicating a critical functional role for recently observed super-diffusive movements of luminal particles in the ER tubules.