The endoplasmic reticulum as an active liquid network

Proc Natl Acad Sci U S A. 2024 Oct 15;121(42):e2409755121. doi: 10.1073/pnas.2409755121. Epub 2024 Oct 11.

Abstract

The peripheral endoplasmic reticulum (ER) forms a dense, interconnected, and constantly evolving network of membrane-bound tubules in eukaryotic cells. While individual structural elements and the morphogens that stabilize them have been described, a quantitative understanding of the dynamic large-scale network topology remains elusive. We develop a physical model of the ER as an active liquid network, governed by a balance of tension-driven shrinking and new tubule growth. This minimalist model gives rise to steady-state network structures with density and rearrangement timescales predicted from the junction mobility and tubule spawning rate. Several parameter-independent geometric features of the liquid network model are shown to be representative of ER architecture in live mammalian cells. The liquid network model connects the timescales of distinct dynamic features such as ring closure and new tubule growth in the ER. Furthermore, it demonstrates how the steady-state network morphology on a cellular scale arises from the balance of microscopic dynamic rearrangements.

Keywords: endoplasmic reticulum; networks; organelle structure; physical modeling; subcellular dynamics.

MeSH terms

  • Animals
  • Endoplasmic Reticulum* / metabolism
  • Humans
  • Models, Biological*