Ionic control of the metastable inner leaflet of the plasma membrane: Fusions natural and artefactual

The phospholipids of the inner and outer leaflets of the plasma membrane face chemically very different environments, and are specialized to serve different needs. While lipids of the outer leaflet are inherently stable in a lamellar (bilayer) phase, the main lipid of the inner layer, phosphatidylethanolamine (PE), does not form a lamellar phase unless evenly mixed with phosphatidylserine (PS−). This mixture can be readily perturbed by factors that include an influx of Ca2+ that chelates the negatively charged PS−, thereby destabilizing PE. The implications of this metastability of the inner leaflet for vesicular trafficking, and experimentally for the isolation of detergent-resistant membrane domains (DRMs) at physiological temperature, are considered.