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TitleSystematic membrane thickness variation across cellular organelles revealed by cryo-ET.
Journal, issue, pagesJ Cell Biol, Vol. 225, Issue 1, Year 2026
Publish dateJan 5, 2026
AuthorsDesislava Glushkova / Stefanie Böhm / Martin Beck /
PubMed AbstractIn eukaryotes, membrane-bound organelles create distinct molecular environments. The compartmentalizing lipid bilayer is a dynamic composite material whose thickness and curvature modulate the ...In eukaryotes, membrane-bound organelles create distinct molecular environments. The compartmentalizing lipid bilayer is a dynamic composite material whose thickness and curvature modulate the structure and function of membrane proteins. In vitro, bilayer thickness correlates with lipid composition. Cellular membranes in situ, however, are continuously remodeled, and the spatial variation of their biophysical properties remains understudied. Here, we present a computational approach to measure local membrane thickness in cryo-electron tomograms. Our analysis of Chlamydomonas reinhardtii and human cells reveals systematic thickness variations within and across organelles. Notably, we observe thickness gradients across the Golgi apparatus that orthogonally support long-standing models of differential sorting of transmembrane proteins based on hydrophobic matching. Our publicly available workflow readily integrates within existing tomogram analysis pipelines and, when applied across experimental systems, provides a quantitative foundation for exploring relationships between membrane thickness and function in native cellular environments.
External linksJ Cell Biol / PubMed:41186573 / PubMed Central
MethodsEM (tomography)
Structure data

EMDB-55308: CryoCARE-denoised tomogram of two HEK293 control cells in close contact
Method: EM (tomography)

EMDB-55310: CryoCARE-denoised tomogram of two cholesterol-depleted HEK293 cells in close contact
Method: EM (tomography)

Source
  • HEK293 (human)

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