The Transport of Charged Molecules across Three Lipid Membranes Investigated with Second Harmonic Generation

Subtle variations in the structure and composition of lipid membranes can have a profound impact on their transport of functional molecules and relevant cell functions. Here, we present a comparison of the permeability of bilayers composed of three lipids: cardiolipin, DOPG (1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol), and POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol)). The adsorption and cross-membrane transport of a charged molecule, D289 (4-(4-diethylaminostyry)-1-methyl-pyridinium iodide), on vesicles composed of the three lipids were monitored by second harmonic generation (SHG) scattering from the vesicle surface. It is revealed that structural mismatching between the saturated and unsaturated alkane chains in POPG leads to relatively loose packing structure in the lipid bilayers, thus providing better permeability compared to unsaturated lipid bilayers (DOPG). This mismatching also weakens the efficiency of cholesterol in rigidifying the lipid bilayers. It is also revealed that the bilayer structure is somewhat disturbed by the surface curvature in small unilamellar vesicles (SUVs) composed of POPG and the conical structured cardiolipin. Such subtle information on the relationship between the lipid structure and the molecular transport capability of the bilayers may provide clues for drug development and other medical and biological studies.

[1]  G. Strangi,et al.  The interaction of tryptophan enantiomers with model membranes is modulated by polar head type and physical state of phospholipids. , 2023, Colloids and surfaces. B, Biointerfaces.

[2]  Q. Yuan,et al.  Measuring the activation energy of the structural evolution in vesicle formation with combined spectroscopic methods and revealing the different ionic effects from Na+ and Ca2+ , 2023, Colloids and Surfaces A: Physicochemical and Engineering Aspects.

[3]  J. Hub,et al.  Passive transport of Ca2+ ions through lipid bilayers imaged by widefield second harmonic microscopy , 2023, Biophysical journal.

[4]  I. Alves,et al.  The impact of lipid polyunsaturation on the physical and mechanical properties of lipid membranes. , 2022, Biochimica et biophysica acta. Biomembranes.

[5]  H. Dai,et al.  Influence of Phase Transitions on Diffusive Molecular Transport Across Biological Membranes. , 2022, Angewandte Chemie.

[6]  M. Bonn,et al.  Phospholipid acyl tail affects lipid headgroup orientation and membrane hydration. , 2022, The Journal of chemical physics.

[7]  Q. Yuan,et al.  Understanding the different cross-membrane transport kinetics of two charged molecules on the DOPG lipid surface with second harmonic generation and MD simulation. , 2022, Soft matter.

[8]  K. Goss,et al.  Impact of cholesterol and sphingomyelin on intrinsic membrane permeability. , 2022, Biochimica et biophysica acta. Biomembranes.

[9]  Neha P. Kamat,et al.  Robust and tunable performance of a cell-free biosensor encapsulated in lipid vesicles , 2022, bioRxiv.

[10]  Q. Yuan,et al.  Evaluating the cross-membrane dynamics of a charged molecule on lipid films with different surface curvature. , 2021, Journal of colloid and interface science.

[11]  Q. Yuan,et al.  Unveiling the Molecular Dynamics in a Living Cell to the Subcellular Organelle Level Using Second-Harmonic Generation Spectroscopy and Microscopy. , 2021, Analytical chemistry.

[12]  Q. Yuan,et al.  Observing the structural variations on binary complex vesicle surfaces and the influence on molecular transportation , 2021 .

[13]  B. Poolman,et al.  Membrane thickness, lipid phase and sterol type are determining factors in the permeability of membranes to small solutes , 2021, Nature Communications.

[14]  Stavroula Sofou,et al.  Daptomycin-Induced Lipid Phases on Model Lipid Bilayers: Effect of Lipid Type and of Lipid Leaflet Order on Membrane Permeability. , 2021, The journal of physical chemistry. B.

[15]  M. Sharifian Gh.,et al.  Recent Experimental Developments in Studying Passive Membrane Transport of Drug Molecules. , 2021, Molecular pharmaceutics.

[16]  B. Paegel,et al.  Chiral Lipid Bilayers are Enantioselectively Permeable , 2021, Nature Chemistry.

[17]  Q. Yuan,et al.  The effect of side group on the dynamic behavior of anthracyclines on DOPG lipid membranes revealed by second harmonic generation and fluorescence , 2021 .

[18]  W. Nau,et al.  Membrane Permeability and Its Activation Energies in Dependence on Analyte, Lipid, and Phase Type Obtained by the Fluorescent Artificial Receptor Membrane Assay. , 2020, ACS sensors.

[19]  N. Priestley,et al.  Curvature-Dependent Binding of Cytochrome c to Cardiolipin. , 2020, Journal of the American Chemical Society.

[20]  J. Valant,et al.  Contribution of headgroup and chain length of glycerophospholipids to thermal stability and permeability of liposomes loaded with calcein. , 2019, Chemistry and physics of lipids.

[21]  J. Hoody,et al.  Cardiolipin Preferentially Partitions to the Inner Leaflet of Mixed Lipid Large Unilamellar Vesicles. , 2019, The journal of physical chemistry. B.

[22]  H. Scheidt,et al.  The Effect of the Alkyl Chain Length of Amphiphilic Ionic Liquids on the Structure and Dynamics of Model Lipid Membranes. , 2019, Langmuir : the ACS journal of surfaces and colloids.

[23]  Revati Kumar,et al.  Molecular Adsorption and Transport at Liposome Surfaces Studied by Molecular Dynamics Simulations and Second Harmonic Generation Spectroscopy. , 2019, The journal of physical chemistry. B.

[24]  S. Roke,et al.  The Chemistry of Lipid Membranes - from Models to Living Systems: A Perspective of Hydration, Surface Potential, Curvature, Confinement and Heterogeneity. , 2019, Journal of the American Chemical Society.

[25]  P. Bassereau,et al.  Membrane curvature induces cardiolipin sorting , 2019, Communications Biology.

[26]  Y. Liang,et al.  Simple physics in and easy manipulating of the interfacial behavior of charged molecules on drug delivery vesicles , 2019, Materials Today Physics.

[27]  Xing Ma,et al.  Understanding the Dynamic Behavior of an Anticancer Drug, Doxorubicin, on a Lipid Membrane Using Multiple Spectroscopic Techniques. , 2019, The journal of physical chemistry. B.

[28]  P. Pohl,et al.  Intrinsic Membrane Permeability to Small Molecules. , 2019, Chemical reviews.

[29]  H. Dai,et al.  Spatially Resolved Membrane Transport in a Single Cell Imaged by Second Harmonic Light Scattering. , 2019, Biochemistry.

[30]  P. Jurkiewicz,et al.  Membrane Lipid Nanodomains. , 2018, Chemical reviews.

[31]  C. Chipot,et al.  Link between Membrane Composition and Permeability to Drugs. , 2018, Journal of chemical theory and computation.

[32]  Q. Yuan,et al.  Lyophobicity may not be the main driving force for long chain surfactants from the bulk phase to the interface. , 2018, Physical chemistry chemical physics : PCCP.

[33]  K. Das,et al.  Effect of Curcumin Addition on the Adsorption and Transport of a Cationic Dye across DPPG-POPG Liposomes Probed by Second Harmonic Spectroscopy. , 2017, Langmuir : the ACS journal of surfaces and colloids.

[34]  L. H. Haber,et al.  Impacts of Salt, Buffer, and Lipid Nature on Molecular Adsorption and Transport in Liposomes As Observed by Second Harmonic Generation , 2017 .

[35]  Q. Cui,et al.  Quantifying the Electrostatics of Polycation-Lipid Bilayer Interactions. , 2017, Journal of the American Chemical Society.

[36]  S. Howorka,et al.  A biomimetic DNA-based channel for the ligand-controlled transport of charged molecular cargo across a biological membrane. , 2016, Nature nanotechnology.

[37]  Xiaolin Cheng,et al.  Structural and mechanical properties of cardiolipin lipid bilayers determined using neutron spin echo, small angle neutron and X-ray scattering, and molecular dynamics simulations. , 2015, Soft matter.

[38]  Zhan-Ting Li,et al.  Voltage-driven reversible insertion into and leaving from a lipid bilayer: tuning transmembrane transport of artificial channels. , 2014, Angewandte Chemie.

[39]  Elsa C. Y. Yan,et al.  Lipid compositions modulate fluidity and stability of bilayers: characterization by surface pressure and sum frequency generation spectroscopy. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[40]  B. Ehrenberg,et al.  The Effect of Lipid Composition on the Permeability of Fluorescent Markers from Photosensitized Membranes , 2013, Photochemistry and photobiology.

[41]  R. Saini,et al.  Effect of curcumin on the diffusion kinetics of a hemicyanine dye, LDS-698, across a lipid bilayer probed by second harmonic spectroscopy. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[42]  Songi Han,et al.  Quantitative analysis of molecular transport across liposomal bilayer by J-mediated 13C Overhauser dynamic nuclear polarization. , 2012, Analytical chemistry.

[43]  Frederick A. Heberle,et al.  Molecular structures of fluid phase phosphatidylglycerol bilayers as determined by small angle neutron and X-ray scattering. , 2012, Biochimica et biophysica acta.

[44]  A. Velázquez‐Campoy,et al.  Kinetics and thermodynamics of chlorpromazine interaction with lipid bilayers: effect of charge and cholesterol. , 2012, Journal of the American Chemical Society.

[45]  Bryan W. Holland,et al.  Scattering density profile model of POPG bilayers as determined by molecular dynamics simulations and small-angle neutron and X-ray scattering experiments. , 2012, The journal of physical chemistry. B.

[46]  Hai-Lung Dai,et al.  Activation of thiols at a silver nanoparticle surface. , 2011, Angewandte Chemie.

[47]  Nathalie Reuter,et al.  Molecular dynamics simulations of mixed acidic/zwitterionic phospholipid bilayers. , 2010, Biophysical journal.

[48]  Li Di,et al.  Coexistence of passive and carrier-mediated processes in drug transport , 2010, Nature Reviews Drug Discovery.

[49]  M. Grzybek,et al.  Measurement of the membrane curvature preference of phospholipids reveals only weak coupling between lipid shape and leaflet curvature , 2009, Proceedings of the National Academy of Sciences.

[50]  K. Eisenthal,et al.  Second harmonic studies of ions crossing liposome membranes in real time. , 2008, The journal of physical chemistry. B.

[51]  Stavroula Sofou,et al.  Heterogeneous domains and membrane permeability in phosphatidylcholine-phosphatidic acid rigid vesicles as a function of pH and lipid chain mismatch. , 2008, Langmuir : the ACS journal of surfaces and colloids.

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

[53]  M. W. Kim,et al.  Temperature effect on the transport dynamics of a small molecule through a liposome bilayer , 2007, The European physical journal. E, Soft matter.

[54]  R. Mészáros,et al.  Adsorption of sodium alkyl sulfate homologues at the air/solution interface. , 2007, The journal of physical chemistry. B.

[55]  J. Kao,et al.  Lipid composition effect on permeability across PAMPA. , 2006, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[56]  A. Yamaguchi,et al.  Longitudinal diffusion behavior of hemicyanine dyes across phospholipid vesicle membranes as studied by second-harmonic generation and fluorescence spectroscopies , 2006, Analytical and bioanalytical chemistry.

[57]  K. Eisenthal,et al.  Antibiotic assisted molecular ion transport across a membrane in real time. , 2005, Faraday discussions.

[58]  Harvey T. McMahon,et al.  Membrane curvature and mechanisms of dynamic cell membrane remodelling , 2005, Nature.

[59]  K. Eisenthal,et al.  Effects of Counterions on Molecular Transport Across Liposome Bilayer: Probed by Second Harmonic Generation , 2001 .

[60]  K. Eisenthal,et al.  Effects of bilayer surface charge density on molecular adsorption and transport across liposome bilayers. , 2001, Biophysical journal.

[61]  K. Eisenthal,et al.  Effect of cholesterol on molecular transport of organic cations across liposome bilayers probed by second harmonic generation. , 2000, Biophysical journal.

[62]  E. Evans,et al.  Water permeability and mechanical strength of polyunsaturated lipid bilayers. , 2000, Biophysical journal.

[63]  K. Eisenthal,et al.  Kinetics of molecular transport across a liposome bilayer , 1998 .

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

[65]  A. Driessen,et al.  Effect of the unsaturation of phospholipid acyl chains on leucine transport of Lactococcus lactis and membrane permeability. , 1992, Biochimica et biophysica acta.

[66]  J. Berg,et al.  Sodium chloride-induced aggregation of dipalmitoylphoshpatidylglycerol small unilamellar vesicles with varying amounts of incorporated cholesterol , 1992 .

[67]  K. Eisenthal,et al.  Energetics of adsorption of neutral and charged molecules at the air/water interface by second harmonic generation: Hydrophobic and solvation effects , 1991 .

[68]  T. McIntosh,et al.  Area per molecule and distribution of water in fully hydrated dilauroylphosphatidylethanolamine bilayers. , 1986, Biochemistry.

[69]  M. Bally,et al.  Production of large unilamellar vesicles by a rapid extrusion procedure: characterization of size distribution, trapped volume and ability to maintain a membrane potential. , 1985, Biochimica et biophysica acta.

[70]  P. Tobback,et al.  Measurement of the glucose permeation rate across phospholipid bilayers using small unilamellar vesicles. Effect of membrane composition and temperature. , 1984, Biochimica et biophysica acta.

[71]  R. Fettiplace.  The influence of the lipid on the water permeability of artificial membranes. , 1978, Biochimica et biophysica acta.

[72]  J. Gier,et al.  The effect of chain length and lipid phase transitions on the selective permeability properties of liposomes. , 1975, Biochimica et biophysica acta.

[73]  R. Dowben,et al.  Formation and properties of thin‐walled phospholipid vesicles , 1969, Journal of cellular physiology.

[74]  C. C. Wang,et al.  Nonlinear optics. , 1966, Applied optics.

[75]  A. F. H. Ward,et al.  Standard Entropy of Adsorption , 1946, Nature.

[76]  T. Xiang,et al.  Permeability of acetic acid across gel and liquid-crystalline lipid bilayers conforms to free-surface-area theory. , 1997, Biophysical journal.