Fluid mechanics of luminal transport in actively contracting endoplasmic reticulum

Abstract:

The Endoplasmic Reticulum (ER), the largest cellular compartment, harbours the machinery for the biogenesis of secretory proteins, lipids, calcium storage/mobilisation and detoxification. It is shaped as layered membranous sheets interconnected with a network of tubules extending throughout the cell. Understanding the influence of the ER morphology dynamics on molecular transport may offer clues to rationalising neuro-pathologies caused by ER morphogen mutations. It remains unclear, however, how the ER facilitates its intra-luminal mobility and homogenises its content, and the minuscule spatial and temporal scales relevant to the ER nanofluidics limit empirical studies. To surmount this barrier, here we exploit the principles of viscous fluid dynamics to generate a theoretical physical model emulating in-silico the content motion in actively contracting nanoscopic tubular networks. The computational model reveals the luminal particle speeds, and their impact in facilitating active transport, of the active contractile behaviour of the different ER components along various time-space parameters. The results of the model indicate that reproducing transport with velocities similar to those reported experimentally in single particle tracking would require unrealistically high values of tubule contraction site length and rate. Considering further nanofluidic scenarios, we show that width contractions of the ER’s flat domains (perinuclear sheets) generate fast-decaying flows with only a short-range effect on luminal transport. Only contraction of peripheral sheets can reproduce experimental measurements, provided they are able to contract fast enough.