Counterion-mediated pattern formation in membranes containing anionic lipids
Slochower DR, Wang YH, Tourdot RW, Radhakrishnan R, Janmey PA. Counterion-mediated pattern formation in membranes containing anionic lipids. Adv Colloid Interface Sci Jan 30 2014;
A simplified representation of a typical mammalian membrane bilayer composition highlighting common lipid families. Cholesterol is shown on both sides of the bilayer, while the extracellular facing leaflet is shown containing PtdCho (gray); the cytosolic leaflet is shown containing negatively charged PtdSer (orange) and PtdIns(4,5)P2 (red) together with the zwitterionic PtdEtn (cyan). The total amount and ratio of lipid species in various cell types can be found in several sources, including ,  and . (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Most lipid components of cell membranes are either neutral, like cholesterol, or zwitterionic, like phosphatidylcholine and sphingomyelin. Very few lipids, such as sphingosine, are cationic at physiological pH. These generally interact only transiently with the lipid bilayer, and their synthetic analogs are often designed to destabilize the membrane for drug or DNA delivery. However, anionic lipids are common in both eukaryotic and prokaryotic cell membranes. The net charge per anionic phospholipid ranges from -1 for the most abundant anionic lipids such as phosphatidylserine, to near -7 for phosphatidylinositol 3,4,5 trisphosphate, although the effective charge depends on many environmental factors. Anionic phospholipids and other negatively charged lipids such as lipopolysaccharides are not randomly distributed in the lipid bilayer, but are highly restricted to specific leaflets of the bilayer and to regions near transmembrane proteins or other organized structures within the plane of the membrane. This review highlights some recent evidence that counterions, in the form of monovalent or divalent metal ions, polyamines, or cationic protein domains, have a large influence on the lateral distribution of anionic lipids within the membrane, and that lateral demixing of anionic lipids has effects on membrane curvature and protein function that are important for biological control.