Plasma membranes: does one model fit all?

Tore Skotland; Kirsten Sandvig

doi:10.1016/j.tcb.2026.03.001

Plasma membranes: does one model fit all?

Trends Cell Biol. 2026 Apr 7:S0962-8924(26)00032-2. doi: 10.1016/j.tcb.2026.03.001. Online ahead of print.

Authors

Tore Skotland¹, Kirsten Sandvig²

Affiliations

¹ Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo 0379, Norway; Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo 0379, Norway. Electronic address: toresko@uio.no.
² Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo 0379, Norway; Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo 0379, Norway; Department of Biosciences, University of Oslo, Oslo 0316, Norway.

PMID: 41951528
DOI: 10.1016/j.tcb.2026.03.001

Abstract

Biological membranes consist of a lipid bilayer with a highly asymmetric distribution of lipids in the two leaflets. This asymmetry is maintained by enzymes whose activities depend on cytosolic ATP and Ca²⁺ concentrations. Recently, a new model for plasma membranes (PMs) was introduced. It is based on studies with human erythrocytes and suggests that there is a 50% overabundance of lipids with two hydrophobic chains in the cytosolic leaflet, compensated by the presence of three times more cholesterol in the outer leaflet. In this opinion article, we discuss the large differences in lipid composition between erythrocytes and other cell types, the assumptions used to reach the new membrane model, and whether this model would fit PMs of other cell types.

Keywords: asymmetry; cholesterol; lipids; membranes; phospholipase A2; sphingomyelinase.

Publication types

Review