Mechanism of shaping membrane nanostructures of endoplasmic reticulum

Ben Zucker, Michael M. Kozlov

Research output: Contribution to journalArticlepeer-review


Recent advances in super-resolution microscopy revealed the previously unknown nanoscopic level of organization of endoplasmic reticulum (ER), one of the most vital intracellular organelles. Membrane nanostructures of 10- to 100-nm intrinsic length scales, which include ER tubular matrices, ER sheet nanoholes, internal membranes of ER exit sites (ERES), and ER transport intermediates, were discovered and imaged in considerable detail, but the physical factors determining their unique geometrical features remained unknown. Here, we proposed and computationally substantiated a common concept for mechanisms of all ER nanostructures based on the membrane intrinsic curvature as a primary factor shaping the membrane and ultra-low membrane tensions as modulators of the membrane configurations. We computationally revealed a common structural motif underlying most of the nanostructures. We predicted the existence of a discrete series of equilibrium configurations of ER tubular matrices and recovered the one corresponding to the observations and favored by ultralow tensions. We modeled the nanohole formation as resulting from a spontaneous collapse of elements of the ER tubular network adjacent to the ER sheet edge and calculated the nanohole dimensions. We proposed the ERES membrane to have a shape of a super flexible membrane bead chain, which acquires random walk configurations unless an ultra-low tension converts it into a straight conformation of a transport intermediate. The adequacy of the proposed concept is supported by a close qualitative and quantitative similarity between the predicted and observed configurations of all four ER nanostructures.

Original languageEnglish
Article numbere2116142119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number1 January
StatePublished - 4 Jan 2022


  • Endoplasmic reticulum
  • Membrane curvature
  • Membrane elasticity
  • Membrane nanostructures
  • Membrane shaping


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