Lipid flip-flop in binary membranes composed of phosphatidylserine and phosphatidylcholine.

The kinetics and thermodynamics of lipid flip-flop in bilayers composed of 1,2-dipalmitoyl-sn-glycero-3-phospho-L-serine (DPPS) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) were studied using sum-frequency vibrational spectroscopy. The kinetics of DSPC and DPPS flip-flop were examined as a function of temperature and bilayer composition. The rate of DSPC flip-flop did not exhibit any significant dependence on bilayer composition while the rate of DPPS flip-flop was inversely dependent on the mole fraction of DPPS. The transition-state thermodynamics for DSPC and DPPS lipids in these mixed bilayers were determined in order to identify the energetic impact of the phosphatidylserine headgroup on lipid flip-flop. The thermodynamics for the DSPC component remained statistically identical to bilayers composed entirely of DSPC. The activation energy for the DPPS component showed a linear correlation with the mole fraction of DPPS for all bilayer compositions. The enthalpy and entropy for DPPS flip-flop did not increase linearly with the fraction of DPPS but did directly correlate with the molecular area. The DPPS component also exhibited enthalpy-entropy compensation which suggests that lipid hydration may play a significant role in membrane dynamics.

[1]  P. Devaux,et al.  Investigation on lipid asymmetry using lipid probes: Comparison between spin-labeled lipids and fluorescent lipids. , 2002, Chemistry and physics of lipids.

[2]  Y. Inoue,et al.  Enthalpy–entropy compensation in complexation of cations with crown ethers and related ligands , 1985 .

[3]  T. E. Thompson,et al.  Transbilayer and interbilayer phospholipid exchange in dimyristoylphosphatidylcholine/dimyristoylphosphatidylethanolamine large unilamellar vesicles. , 1991, Biochemistry.

[4]  M. Kozlov,et al.  Flippase Activity Detected with Unlabeled Lipids by Shape Changes of Giant Unilamellar Vesicles* , 2007, Journal of Biological Chemistry.

[5]  Bradley D. Smith,et al.  Facilitated phosphatidylserine flip-flop across vesicle and cell membranes using urea-derived synthetic translocases. , 2004, Organic & biomolecular chemistry.

[6]  P. Devaux,et al.  Protein involvement in transmembrane lipid asymmetry. , 1992, Annual review of biophysics and biomolecular structure.

[7]  E Gratton,et al.  A correlation between lipid domain shape and binary phospholipid mixture composition in free standing bilayers: A two-photon fluorescence microscopy study. , 2000, Biophysical journal.

[8]  A. Herrmann,et al.  Tracking down lipid flippases and their biological functions , 2004, Journal of Cell Science.

[9]  J. Conboy,et al.  Direct measurement of the transbilayer movement of phospholipids by sum-frequency vibrational spectroscopy. , 2004, Journal of the American Chemical Society.

[10]  Wan-Chen Lin,et al.  Lipid asymmetry in DLPC/DSPC-supported lipid bilayers: a combined AFM and fluorescence microscopy study. , 2006, Biophysical journal.

[11]  F. Sharom,et al.  Phospholipid flippase activity of the reconstituted P-glycoprotein multidrug transporter. , 2001, Biochemistry.

[12]  P. Devaux,et al.  Static and dynamic lipid asymmetry in cell membranes. , 1991, Biochemistry.

[13]  J. Freyssinet,et al.  Scott syndrome, characterized by impaired transmembrane migration of procoagulant phosphatidylserine and hemorrhagic complications, is an inherited disorder. , 1996, Blood.

[14]  I. Vavasour,et al.  Smoothed acyl chain orientational order parameter profiles in dimyristoylphosphatidylcholine-distearoylphosphatidylcholine mixtures: a 2H-NMR study. , 1995, Biophysical journal.

[15]  M. Petri,et al.  Surface blebs on apoptotic cells are sites of enhanced procoagulant activity: implications for coagulation events and antigenic spread in systemic lupus erythematosus. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[16]  K. Eisenthal,et al.  Liquid Interfaces Probed by Second-Harmonic and Sum-Frequency Spectroscopy. , 1996, Chemical reviews.

[17]  J. Conboy,et al.  1,2-diacyl-phosphatidylcholine flip-flop measured directly by sum-frequency vibrational spectroscopy. , 2005, Biophysical journal.

[18]  A. Schroit,et al.  Aminophospholipid asymmetry: A matter of life and death. , 2003, Annual review of physiology.

[19]  I. López-Montero,et al.  Rapid Transbilayer Movement of Ceramides in Phospholipid Vesicles and in Human Erythrocytes* , 2005, Journal of Biological Chemistry.

[20]  J. Conboy,et al.  Kinetics and thermodynamics of flip-flop in binary phospholipid membranes measured by sum-frequency vibrational spectroscopy. , 2009, Biochemistry.

[21]  M. Kozlov,et al.  How lipid flippases can modulate membrane structure. , 2008, Biochimica et biophysica acta.

[22]  Wilfred F. van Gunsteren,et al.  Computer simulation studies on the solvation of aliphatic hydrocarbons in 6.9 M aqueous urea solution , 2004 .

[23]  R. Molday,et al.  Localization, Purification, and Functional Reconstitution of the P4-ATPase Atp8a2, a Phosphatidylserine Flippase in Photoreceptor Disc Membranes* , 2009, The Journal of Biological Chemistry.

[24]  A. Schroit,et al.  Insertion of fluorescent phosphatidylserine into the plasma membrane of red blood cells. Recognition by autologous macrophages. , 1983, The Journal of biological chemistry.

[25]  J. O. D. Kamp,et al.  LIPID ASYMMETRY IN MEMBRANES , 1979 .

[26]  A. Braibanti,et al.  Entropy/enthalpy compensation: hydrophobic effect, micelles and protein complexes , 2004 .

[27]  J. Savill Apoptosis in resolution of inflammation , 1997, Journal of leukocyte biology.

[28]  V. Fadok,et al.  Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. , 1992, Journal of immunology.

[29]  J. Conboy,et al.  Phase Behavior of Planar Supported Lipid Membranes Composed of Cholesterol and 1,2-Distearoyl-sn-Glycerol-3-Phosphocholine Examined by Sum-Frequency Vibrational Spectroscopy. , 2009, Vibrational Spectroscopy.

[30]  M. Nakano,et al.  Determination of interbilayer and transbilayer lipid transfers by time-resolved small-angle neutron scattering. , 2007, Physical review letters.

[31]  Paul B. Davies,et al.  Implementing the Theory of Sum Frequency Generation Vibrational Spectroscopy: A Tutorial Review , 2005 .

[32]  T. Nii,et al.  Properties of various phospholipid mixtures as emulsifiers or dispersing agents in nanoparticle drug carrier preparations. , 2005, Colloids and surfaces. B, Biointerfaces.

[33]  Y. Nishizuka Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. , 1992, Science.

[34]  M. J. Swamy,et al.  Isothermal Titration Calorimetric Studies on the Interaction of the Major Bovine Seminal Plasma Protein, PDC-109 with Phospholipid Membranes , 2011, PloS one.

[35]  V. Fadok,et al.  Apoptotic cell removal , 2001, Current Biology.

[36]  D. Discher,et al.  Detection of altered membrane phospholipid asymmetry in subpopulations of human red blood cells using fluorescently labeled annexin V. , 1996, Blood.

[37]  F. Sharom,et al.  Lipid bilayer properties control membrane partitioning, binding, and transport of p-glycoprotein substrates. , 2013, Biochemistry.

[38]  R. Kornberg,et al.  Inside-outside transitions of phospholipids in vesicle membranes. , 1971, Biochemistry.

[39]  Zhan Chen,et al.  SUM FREQUENCY GENERATION VIBRATIONAL SPECTROSCOPY STUDIES ON MOLECULAR CONFORMATION AND ORIENTATION OF BIOLOGICAL MOLECULES AT INTERFACES , 2005 .

[40]  J. Conboy,et al.  Lateral pressure dependence of the phospholipid transmembrane diffusion rate in planar-supported lipid bilayers. , 2008, Biophysical journal.

[41]  D. Daleke,et al.  Hyperglycemia induces a loss of phospholipid asymmetry in human erythrocytes. , 1993, Biochemistry.

[42]  J. Conboy,et al.  Electrostatic induction of lipid asymmetry. , 2011, Journal of the American Chemical Society.

[43]  C. Mold,et al.  Activation of the alternative complement pathway by exposure of phosphatidylethanolamine and phosphatidylserine on erythrocytes from sickle cell disease patients. , 1993, The Journal of clinical investigation.

[44]  K. Sakurai,et al.  Apoptosis and mitochondrial damage in INS-1 cells treated with alloxan. , 2001, Biological & pharmaceutical bulletin.

[45]  Qing-xiang Guo,et al.  Isokinetic relationship, isoequilibrium relationship, and enthalpy-entropy compensation. , 2001, Chemical reviews.

[46]  S. Grinstein,et al.  Phosphatidylserine dynamics in cellular membranes , 2012, Molecular biology of the cell.

[47]  M. J. Scott,et al.  A microcalorimetric study of the interaction of phospholipid liposomes with colloidal titanium dioxide and silica: an example of enthalpy–entropy compensation , 2002 .

[48]  J. Conboy,et al.  Structure of a gel phase lipid bilayer prepared by the Langmuir-Blodgett/Langmuir-Schaefer method characterized by sum-frequency vibrational spectroscopy. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[49]  Jason G. Kay,et al.  Sensing Phosphatidylserine in Cellular Membranes , 2011, Sensors.

[50]  P. Devaux,et al.  Transmembrane diffusion of fluorescent phospholipids in human erythrocytes. , 1991, Chemistry and physics of lipids.

[51]  H. Hemker,et al.  Generation of prothrombin-converting activity and the exposure of phosphatidylserine at the outer surface of platelets. , 1982, European journal of biochemistry.

[52]  J. Conboy,et al.  Free energy and entropy of activation for phospholipid flip-flop in planar supported lipid bilayers. , 2010, The journal of physical chemistry. B.

[53]  M. Tsujimoto,et al.  Asymmetric distribution of phospholipids in biomembranes. , 2006, Biological & pharmaceutical bulletin.

[54]  G. Meer,et al.  Membrane lipids: where they are and how they behave , 2008, Nature Reviews Molecular Cell Biology.

[55]  P. Comfurius,et al.  Scott syndrome, a bleeding disorder caused by defective scrambling of membrane phospholipids. , 2004, Biochimica et biophysica acta.