pH modulation of transport properties of alamethicin oligomers inserted in zwitterionic-based artificial lipid membranes

Chiriac, Roxana; Luchian, Tudor

doi:10.1016/j.bpc.2007.08.009

Cited by 18 publications

(16 citation statements)

References 44 publications

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“…The effective pKa of Glu 18 in that study was around 4.5-5, indicating weak interactions between the Glu 18 residues and that at neutral pH all Glu 18 are ionized. This is in agreement with the work of Chiriac and Luchian [68]. In the present simulations Glu18 was unprotonated.…”

Section: Discussionsupporting

confidence: 94%

A thermodynamic approach to alamethicin pore formation

Rahaman

Lazaridis

2014

Biochimica et Biophysica Acta (BBA) - Biomembranes

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The structure and energetics of alamethicin Rf30 monomer to nonamer in cylindrical pores of 5 to 11 Å radius are investigated using molecular dynamics simulations in an implicit membrane model that includes the free energy cost of acyl chain hydrophobic area exposure. Stable, low energy pores are obtained for certain combinations of radius and oligomeric number. The trimer and the tetramer formed 6 Å pores that appear closed while the larger oligomers formed open pores at their optimal radius. The hexamer in an 8 Å pore and the octamer in an 11 Å pore give the lowest effective energy per monomer. However, all oligomers beyond the pentamer have comparable energies, consistent with the observation of multiple conductance levels. The results are consistent with the widely accepted “barrel-stave” model. The N terminal portion of the molecule exhibits smaller tilt with respect to the membrane normal than the C terminal portion, resulting in a pore shape that is a hybrid between a funnel and an hourglass. Transmembrane voltage has little effect on the structure of the oligomers but enhances or decreases their stability depending on its orientation. Antiparallel bundles are lower in energy than the commonly accepted parallel ones and could be present under certain experimental conditions. Dry aggregates (without an aqueous pore) have lower average effective energy than the corresponding aggregates in a pore, suggesting that alamethicin pores may be excited states that are stabilized in part by voltage and in part by the ion flow itself.

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Section: Discussionsupporting

confidence: 94%

A thermodynamic approach to alamethicin pore formation

Rahaman

Lazaridis

2014

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…79 Because pH plays a crucial role in modulating the electric characteristics of zwitterionic-based lipid membranes, changes in pH have been used to modulate the transport properties of alamethicin oligomers inserted in zwitterionic-based model lipid membranes. 75 In addition, earlier studies have indicated that high pH values increased the open-state probability of the channel of Entamoeba histolytica , which has a mechanism of action similar to alamethicin. 80 With this in mind, we modulated the membrane potential by changing the pH of the subphase in contact with the lipid bilayer.…”

Section: Introductionmentioning

confidence: 98%

“…72–74 In addition to an external electric field, protons and hydroxides (or pH variations) can also effectively modulate lipid membrane potential by altering surface charge and dipole potential. 75–79 Upon exposing a lipid membrane to aqueous solutions of varying pH, the phosphate and choline groups of lipid molecules may change charge distribution at the membrane interface, resulting in alterations of their Debye length, membrane surface charge density, and zeta potential. 75–79 This can lead to a change in membrane potential and an increase in channel protein conductance.…”

Section: Introductionmentioning

confidence: 99%

“…75–79 Upon exposing a lipid membrane to aqueous solutions of varying pH, the phosphate and choline groups of lipid molecules may change charge distribution at the membrane interface, resulting in alterations of their Debye length, membrane surface charge density, and zeta potential. 75–79 This can lead to a change in membrane potential and an increase in channel protein conductance. 79 Because pH plays a crucial role in modulating the electric characteristics of zwitterionic-based lipid membranes, changes in pH have been used to modulate the transport properties of alamethicin oligomers inserted in zwitterionic-based model lipid membranes.…”

Section: Introductionmentioning

confidence: 99%

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Observing a Model Ion Channel Gating Action in Model Cell Membranes in Real Time in Situ: Membrane Potential Change Induced Alamethicin Orientation Change

Wei

et al. 2012

J. Am. Chem. Soc.

129

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Ion channels play crucial roles in transport and regulatory functions of living cells. Understanding the gating mechanisms of these channels is important to understanding and treating diseases that have been linked to ion channels. One potential model peptide for studying the mechanism of ion channel gating is alamethicin, which adopts a split alpha/310 helix structure and responds to changes in electric potential. In this study, sum frequency generation vibrational spectroscopy (SFG-VS), supplemented by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), has been applied to characterize interactions between alamethicin (a model for larger channel proteins) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayers in the presence of an electric potential across the membrane. The membrane potential difference was controlled by changing the pH of the solution in contact with the bilayer, and measured using fluorescence spectroscopy. The orientation angle of alamethicin in POPC lipid bilayers was then determined at different pH values using polarized SFG amide I spectra. Assuming that all molecules adopt the same orientation (a δ distribution), at pH=6.7 the α-helix at the N-terminus and the 310 helix at the C-terminus tilt at about 72° (θ1) and 50° (θ2) versus the surface normal, respectively. When pH increases to 11.9, θ1 and θ2 decrease to 56.5° and 45°, respectively. The δ distribution assumption was verified using a combination of SFG and ATR-FTIR measurements, which showed a quite narrow distribution in the angle of θ1 for both pH conditions. This indicates that all alamethicin molecules at the surface adopt a nearly identical orientation in POPC lipid bilayers. The localized pH change in proximity to the bilayer modulates the membrane potential and thus induces a decrease in both the tilt and bend angles of the two helices in alamethicin. This is the first reported application of SFG to the study of model ion channel gating mechanisms in model cell membranes.

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“…Mueller technique, as previously described [25,36]. The lipid used was L-α-phosphatidylcholine (Fluka, code 61755), and sodium chloride salt solutions were buffered at a pH value of 2.8 in 5 mM MES buffer (Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

Influence of membrane potentials upon reversible protonation of acidic residues from the OmpF eyelet

Asandei

Mereuta

Luchian

2008

Biophysical Chemistry

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. Influence of membrane potentials upon reversible protonation of acidic residues from the OmpF eyelet. Biophysical Chemistry, Elsevier, 2008, 135 (1- This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T In this research we employed single-molecule electric recording techniques to investigate effects of the transmembrane and dipole potential on the reversible protonation of acidic residues from the constriction zone of the OmpF porin. Our results support the paradigm according to which the protonation state of aspartate 113 and glutamate 117 residues from the constriction region of OmpF is influenced by the electric potential profile, via an augmentation of the local concentration of protons near these residues mediated by increasing negative transmembrane potentials. We propose that at constant bulk pH, pK a values for protons binding at these residues increase as the applied transmembrane potential increases in its negative values. Our data demonstrate that the apparent pK a for proton binding of the acidic aminoacids from the constriction region of OmpF is ionic strengthdependent, in the sense that a low ionic strength in the aqueous phase promotes the increase of the protonation reaction rate of such residues, at any given holding potential. Supplementary, we present evidence suggesting that lower values of the membrane dipole potential lead to an increase in the values of the 'on' rate of the eyelet acidic residues protonation, caused by an elevation of the local concentration of hydrogen ions. Altogether, these results come to support the paradigm according to which transmembrane and dipole potentials are critical parameters for the titration behavior of protein sites embedded lipid membranes. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT ACCEPTED MANUSCRIPT

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pH modulation of transport properties of alamethicin oligomers inserted in zwitterionic-based artificial lipid membranes

Cited by 18 publications

References 44 publications

A thermodynamic approach to alamethicin pore formation

A thermodynamic approach to alamethicin pore formation

Observing a Model Ion Channel Gating Action in Model Cell Membranes in Real Time in Situ: Membrane Potential Change Induced Alamethicin Orientation Change

Influence of membrane potentials upon reversible protonation of acidic residues from the OmpF eyelet

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