Probing the lipid membrane dipole potential by atomic force microscopy.

The electrostatic properties of biological membranes can be described by three parameters: the transmembrane potential, the membrane surface potential, and the membrane dipole potential. The first two are well characterized in terms of their magnitudes and biological effects. The dipole potential, however, is not well characterized. Various methods to measure the membrane dipole potential indirectly yield different values, and there is not even agreement on the source of the membrane dipole moment. This ambiguity impedes investigations into the biological effects of the membrane dipole moment, which should be substantial considering the large interfacial fields with which it is associated. Electrostatic analysis of phosphatidylcholine lipid membranes with the atomic force microscope reveals a repulsive force between the negatively charged probe tips and the zwitterionic lipids. This unexpected interaction has been analyzed quantitatively to reveal that the repulsion is due to a weak external field created by the internal membrane dipole potential. The analysis yields a dipole moment of 1.5 Debye per lipid with a dipole potential of +275 mV for supported phosphatidylcholine membranes. This new ability to quantitatively measure the membrane dipole moment in a noninvasive manner with nanometer scale spatial resolution will be useful in identifying the biological effects of the dipole potential.

[1]  R. MacKinnon,et al.  Phospholipids and the origin of cationic gating charges in voltage sensors , 2006, Nature.

[2]  R. Clarke,et al.  Optical detection of membrane dipole potential: avoidance of fluidity and dye-induced effects. , 1997, Biochimica et biophysica acta.

[3]  M. Belaya,et al.  Electric Double Layer near Soft Permeable Interfaces. 1. Local Electrostatic , 1994 .

[4]  Ronald J Clarke,et al.  Hydrophobic ion hydration and the magnitude of the dipole potential. , 2002, Biophysical journal.

[5]  G. Cevc,et al.  Membrane electrostatics. , 1990, Biochimica et biophysica acta.

[6]  N. Turner,et al.  Electric field strength of membrane lipids from vertebrate species: membrane lipid composition and Na+-K+-ATPase molecular activity. , 2005, American journal of physiology. Regulatory, integrative and comparative physiology.

[7]  P. O'shea,et al.  Intermolecular interactions with/within cell membranes and the trinity of membrane potentials: kinetics and imaging. , 2003, Biochemical Society transactions.

[8]  D. Murray,et al.  Plasma membrane phosphoinositide organization by protein electrostatics , 2005, Nature.

[9]  Y. Mély,et al.  Ultrasensitive two-color fluorescence probes for dipole potential in phospholipid membranes , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[10]  L M Loew,et al.  Dual-wavelength ratiometric fluorescence measurement of the membrane dipole potential. , 1994, Biophysical journal.

[11]  T. Cover,et al.  Targeting of Helicobacter pylori vacuolating toxin to lipid raft membrane domains analysed by atomic force microscopy. , 2004, The Biochemical journal.

[12]  P. Gurnev,et al.  Effect of agents modifying the membrane dipole potential on properties of syringomycin E channels. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[13]  J. Israelachvili.  Intermolecular and surface forces , 1985 .

[14]  R. Clarke.  The dipole potential of phospholipid membranes and methods for its detection. , 2001, Advances in colloid and interface science.

[15]  J. Ruysschaert,et al.  Characterization of the Sequence of Interactions of the Fusion Domain of the Simian Immunodeficiency Virus with Membranes , 1999, The Journal of Biological Chemistry.

[16]  D. Busath,et al.  Modulation of Lipid Bilayer Interfacial Dipole Potential by Phloretin, RH421, and 6-Ketocholestanol as Probed by Gramicidin Channel Conductance , 2003 .

[17]  Fred J Sigworth,et al.  Using cryo-EM to measure the dipole potential of a lipid membrane , 2006, Proceedings of the National Academy of Sciences.

[18]  D. Haydon,et al.  Surface charge, surface dipoles and membrane conductance. , 1973, Biochimica et biophysica acta.

[19]  A. C. Hillier,et al.  Measurement of Double-Layer Forces at the Electrode/Electrolyte Interface Using the Atomic Force Microscope: Potential and Anion Dependent Interactions , 1996 .

[20]  J. Hafner,et al.  Fluid electric force microscopy for charge density mapping in biological systems , 2003 .

[21]  H. Brockman,et al.  Dipole potential of lipid membranes. , 1994, Chemistry and physics of lipids.

[22]  Sagar A. Pandit,et al.  Aqueous solutions next to phospholipid membrane surfaces: insights from simulations. , 2006, Chemical reviews.

[23]  Sagar A. Pandit,et al.  Molecular dynamics simulation of a dipalmitoylphosphatidylcholine bilayer with NaCl. , 2003, Biophysical journal.

[24]  J. Cladera,et al.  Intramembrane molecular dipoles affect the membrane insertion and folding of a model amphiphilic peptide. , 1998, Biophysical journal.

[25]  D. Cafiso,et al.  Internal electrostatic potentials in bilayers: measuring and controlling dipole potentials in lipid vesicles. , 1993, Biophysical journal.

[26]  E. Liberman,et al.  [Permeability of bimolecular phospholipid membranes for fat-soluble ions]. , 1969, Biofizika.

[27]  J. Hafner,et al.  Quantitative membrane electrostatics with the atomic force microscope. , 2007, Biophysical journal.

[28]  R. MacKinnon.  Voltage Sensor Meets Lipid Membrane , 2004, Science.

[29]  S. McLaughlin,et al.  Adsorption of monovalent cations to bilayer membranes containing negative phospholipids. , 1979, Biochemistry.

[30]  Richard M. Pashley,et al.  Hydration forces between mica surfaces in electrolyte solutions , 1982 .

[31]  B. Maggio,et al.  Modulation of phospholipase A2 by electrostatic fields and dipole potential of glycosphingolipids in monolayers. , 1999, Journal of lipid research.

[32]  M. Edidin.  The state of lipid rafts: from model membranes to cells. , 2003, Annual review of biophysics and biomolecular structure.

[33]  P. Hansma,et al.  A nondestructive method for determining the spring constant of cantilevers for scanning force microscopy , 1993 .

[34]  J. Cladera,et al.  Effects of the Membrane Dipole Potential on the Interaction of Saquinavir with Phospholipid Membranes and Plasma Membrane Receptors of Caco-2 Cells* , 2001, The Journal of Biological Chemistry.