Fluid mechanics of luminal transport in actively contracting endoplasmic reticulum
The endoplasmic reticulum (ER), the largest cellular compartment, harbours the machinery for the biogenesis of secretory proteins and lipids, calcium storage/mobilisation, and detoxification. It is shaped as layered membranous sheets interconnected with a network of tubules extending throughout the...
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eLife Sciences Publications Ltd
2024-12-01
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| Online Access: | https://elifesciences.org/articles/93518 |
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| _version_ | 1846124572402778112 |
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| author | Pyae Hein Htet Edward Avezov Eric Lauga |
| author_facet | Pyae Hein Htet Edward Avezov Eric Lauga |
| author_sort | Pyae Hein Htet |
| collection | DOAJ |
| description | The endoplasmic reticulum (ER), the largest cellular compartment, harbours the machinery for the biogenesis of secretory proteins and 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. It has been recently proposed that intra-luminal transport may be enabled by active contractions of ER tubules. To surmount the barriers to empirical studies of the minuscule spatial and temporal scales relevant to ER nanofluidics, 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 local flows with only a short-range effect on luminal transport. Only contractions of peripheral sheets can reproduce experimental measurements, provided they are able to contract fast enough. |
| format | Article |
| id | doaj-art-4f02891497c548459d3732aab6a151ad |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-4f02891497c548459d3732aab6a151ad2024-12-13T15:51:24ZengeLife Sciences Publications LtdeLife2050-084X2024-12-011310.7554/eLife.93518Fluid mechanics of luminal transport in actively contracting endoplasmic reticulumPyae Hein Htet0https://orcid.org/0000-0001-5068-9828Edward Avezov1https://orcid.org/0000-0002-2894-0585Eric Lauga2https://orcid.org/0000-0002-8916-2545Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge, United KingdomUK Dementia Research Institute at University of Cambridge, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United KingdomDepartment of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge, United KingdomThe endoplasmic reticulum (ER), the largest cellular compartment, harbours the machinery for the biogenesis of secretory proteins and 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. It has been recently proposed that intra-luminal transport may be enabled by active contractions of ER tubules. To surmount the barriers to empirical studies of the minuscule spatial and temporal scales relevant to ER nanofluidics, 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 local flows with only a short-range effect on luminal transport. Only contractions of peripheral sheets can reproduce experimental measurements, provided they are able to contract fast enough.https://elifesciences.org/articles/93518endoplasmic reticulumintracellular transportnetworksfluid dynamicsbiological fluid mechanicsorganelles |
| spellingShingle | Pyae Hein Htet Edward Avezov Eric Lauga Fluid mechanics of luminal transport in actively contracting endoplasmic reticulum eLife endoplasmic reticulum intracellular transport networks fluid dynamics biological fluid mechanics organelles |
| title | Fluid mechanics of luminal transport in actively contracting endoplasmic reticulum |
| title_full | Fluid mechanics of luminal transport in actively contracting endoplasmic reticulum |
| title_fullStr | Fluid mechanics of luminal transport in actively contracting endoplasmic reticulum |
| title_full_unstemmed | Fluid mechanics of luminal transport in actively contracting endoplasmic reticulum |
| title_short | Fluid mechanics of luminal transport in actively contracting endoplasmic reticulum |
| title_sort | fluid mechanics of luminal transport in actively contracting endoplasmic reticulum |
| topic | endoplasmic reticulum intracellular transport networks fluid dynamics biological fluid mechanics organelles |
| url | https://elifesciences.org/articles/93518 |
| work_keys_str_mv | AT pyaeheinhtet fluidmechanicsofluminaltransportinactivelycontractingendoplasmicreticulum AT edwardavezov fluidmechanicsofluminaltransportinactivelycontractingendoplasmicreticulum AT ericlauga fluidmechanicsofluminaltransportinactivelycontractingendoplasmicreticulum |