New isolation method maps the lipid makeup of the endoplasmic reticulum

An international team of molecular biologists and bioinformaticians has isolated the endoplasmic reticulum from mammalian cells and established the lipid composition of its membrane, publishing the results in EMBO Reports. The work, led by first author Aamna Jain, a doctoral researcher supervised by Robert Ernst, professor of molecular biology at Saarland University, adapted a purification technology originally developed for yeast so that it could be applied to mammalian cells, specifically HEK293T cells. The study, titled Mammalian MemPrep establishes the lipid composition of ER membranes in HEK293T cells, appeared online on 14 October 2026.

The endoplasmic reticulum is one of the cell’s most important organelles, a dynamic network extending throughout the cell that plays an essential role in cell growth. It is also the compartment where the cell produces most of its membrane proteins and synthesizes membrane lipids. Because a wide range of complex metabolic disorders originate in this organelle, the researchers argue that understanding how it responds to metabolic imbalances is a prerequisite for developing effective, targeted therapies. Ernst describes the endoplasmic reticulum as a highly sensitive metabolic sensor that responds both to cancer and to chronic inflammatory diseases such as rheumatoid arthritis and Crohn’s disease.

The central technical challenge was purity. The endoplasmic reticulum is physically connected to virtually every other organelle in the cell to enable rapid organelle communication, so any preparation inevitably carries contaminants from neighbouring compartments. To obtain clean samples, the team first had to break these membrane connections before using antibodies to extract the endoplasmic reticulum. By refining their MemPrep technology, which was originally developed for the model organism yeast, the researchers succeeded in isolating and characterizing the organelle from mammalian cells, allowing them to profile its membrane with state-of-the-art analytical techniques.

With pure preparations in hand, the team can now investigate in detail how the endoplasmic reticulum responds to metabolic stress and identify potential ways of restoring metabolic balance in stressed cells. The study also delivered a result the authors describe as surprising for cell biologists: different regions of the endoplasmic reticulum, whether they form tubules or sheets, are composed of the same membrane lipids. This was unexpected because these structurally distinct regions are clearly stabilized by different proteins, yet their membrane-lipid composition remains unchanged, suggesting that protein composition rather than lipid makeup distinguishes the organelle’s subregions.

Bioinformatics contributed a complementary layer to the mapping effort. Volkhard Helms, professor of bioinformatics at Saarland University, and research associate Mohamed Elmofty developed the HelixHarbor web application, which was used to identify distinctive features of membrane proteins in the endoplasmic reticulum. Their findings were subsequently generalized with the assistance of Joseph Lorent, an expert in sequence analysis at the Louvain Drug Research Institute at UCLouvain in Belgium, extending the protein-level characterization beyond the original dataset.

For Ernst, mapping the cell and its organelles is a step towards creating a digital twin of the cell: a computer model that can simulate cellular processes and generate predictions testable in the laboratory. The results of those experiments can then be used to refine the digital twin in a continuous iterative process. The study was conducted as part of the Frankfurt SCALE Cluster of Excellence, the Subcellular Architecture of Life cluster at Goethe University Frankfurt, where Ernst and Dora Tang, professor of synthetic biology at Saarland University, are external members of the core team. Their aim within the cluster is to develop digital and synthetic twins of cellular compartments to model cell behaviour using increasingly realistic digital representations.

Subject of Research: Isolation and lipid profiling of the endoplasmic reticulum membrane in mammalian HEK293T cells

Article Title: Mapping the cell: International research team investigates the endoplasmic reticulum

Article References: Mapping the cell: International research team investigates the endoplasmic reticulum. Original publication (Bibliographic details unavailable.)

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Keywords: cell biology, endoplasmic reticulum, membrane lipids, MemPrep, organelles, digital twin, EMBO Reports, metabolic disorders, Mapping, cell, International, research