title: Counterion-mediated pattern formation in membranes containing anionic lipids.
abstract: 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.
authors.affiliation: Graduate Group in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Slochower
authors.affiliation: Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Yu-Hsiu
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Tourdot
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Radhakrishnan
authors.affiliation: Graduate Group in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Departments of Physiology and Physics, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Janmey
mesh_terms: D000818:Animals; D000838:Anions / Q000737:chemistry / Q000378:metabolism; D055592:Biophysical Phenomena; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008567:Membranes, Artificial; D008954:Models, Biological; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D055672:Static Electricity; D013499:Surface Properties
chemical_list: D000838:Anions; D008051:Lipid Bilayers; D008565:Membrane Proteins; D008567:Membranes, Artificial; D010743:Phospholipids
keywords: Anionic phospholipids; Divalent counterions; Membrane patterning