Amphotericin B induces interdigitation of apolipoprotein stabilized nanodisk bilayers

Thanh Son Nguyen, Paul M M Weers, Vincent Raussens, Zhen Wang, Gang Ren, Todd Sulchek, Paul D. Hoeprich, Robert O. Ryan

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Amphotericin B nanodisks (AMB-ND) are ternary complexes of AMB, phospholipid and apolipoprotein organized as discrete nanometer scale disk-shaped bilayers. In gel filtration chromatography experiments, empty ND lacking AMB elute as a single population of particles with a molecular weight in the range of 200 kDa. AMB-ND formulated at a 4:1 phospholipid:AMB weight ratio separated into two peaks. One peak eluted at the position of control ND lacking AMB while the second peak, containing all of the AMB present in the original sample, eluted in the void volume. When ND prepared with increased AMB were subjected to gel filtration chromatography an increased proportion of phospholipid and apolipoprotein was recovered in the void volume with AMB. Native gradient gel electrophoresis corroborated the gel filtration chromatography data and electron microscopy studies revealed an AMB concentration-dependent heterogeneity in ND particle size. Stability studies revealed that introduction of AMB into ND decreases the ability of apoA-I to resist denaturation. Atomic force microscopy experiments showed that AMB induces compression of ND bilayer thickness while infrared spectroscopy analysis revealed that the presence of AMB does not induce extreme lipid disorder or alter the mean angle of the molecular axis along fatty acyl chains of ND phospholipids. Taken together the results are consistent with AMB-induced bilayer interdigitation, a phenomenon that likely contributes to AMB-dependent pore formation in susceptible membranes.

Original languageEnglish (US)
Pages (from-to)303-312
Number of pages10
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1778
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

Fingerprint

Apolipoproteins
Amphotericin B
Phospholipids
Chromatography
Gels
Gel Chromatography
Denaturation
Atomic Force Microscopy
Apolipoprotein A-I
Electrophoresis
Particle Size
Electron microscopy
Infrared spectroscopy
Atomic force microscopy
Spectrum Analysis
Electron Microscopy
Molecular Weight
Experiments
Molecular weight
Particle size

Keywords

  • Amphotericin B
  • Atomic force microscopy
  • Infrared spectroscopy
  • Interdigitation
  • Membrane
  • Nanodisk

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Biophysics

Cite this

Nguyen, T. S., Weers, P. M. M., Raussens, V., Wang, Z., Ren, G., Sulchek, T., ... Ryan, R. O. (2008). Amphotericin B induces interdigitation of apolipoprotein stabilized nanodisk bilayers. Biochimica et Biophysica Acta - Biomembranes, 1778(1), 303-312. https://doi.org/10.1016/j.bbamem.2007.10.005

Amphotericin B induces interdigitation of apolipoprotein stabilized nanodisk bilayers. / Nguyen, Thanh Son; Weers, Paul M M; Raussens, Vincent; Wang, Zhen; Ren, Gang; Sulchek, Todd; Hoeprich, Paul D.; Ryan, Robert O.

In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1778, No. 1, 01.2008, p. 303-312.

Research output: Contribution to journalArticle

Nguyen, TS, Weers, PMM, Raussens, V, Wang, Z, Ren, G, Sulchek, T, Hoeprich, PD & Ryan, RO 2008, 'Amphotericin B induces interdigitation of apolipoprotein stabilized nanodisk bilayers', Biochimica et Biophysica Acta - Biomembranes, vol. 1778, no. 1, pp. 303-312. https://doi.org/10.1016/j.bbamem.2007.10.005
Nguyen, Thanh Son ; Weers, Paul M M ; Raussens, Vincent ; Wang, Zhen ; Ren, Gang ; Sulchek, Todd ; Hoeprich, Paul D. ; Ryan, Robert O. / Amphotericin B induces interdigitation of apolipoprotein stabilized nanodisk bilayers. In: Biochimica et Biophysica Acta - Biomembranes. 2008 ; Vol. 1778, No. 1. pp. 303-312.
@article{56944ec824554597873ce440367b892f,
title = "Amphotericin B induces interdigitation of apolipoprotein stabilized nanodisk bilayers",
abstract = "Amphotericin B nanodisks (AMB-ND) are ternary complexes of AMB, phospholipid and apolipoprotein organized as discrete nanometer scale disk-shaped bilayers. In gel filtration chromatography experiments, empty ND lacking AMB elute as a single population of particles with a molecular weight in the range of 200 kDa. AMB-ND formulated at a 4:1 phospholipid:AMB weight ratio separated into two peaks. One peak eluted at the position of control ND lacking AMB while the second peak, containing all of the AMB present in the original sample, eluted in the void volume. When ND prepared with increased AMB were subjected to gel filtration chromatography an increased proportion of phospholipid and apolipoprotein was recovered in the void volume with AMB. Native gradient gel electrophoresis corroborated the gel filtration chromatography data and electron microscopy studies revealed an AMB concentration-dependent heterogeneity in ND particle size. Stability studies revealed that introduction of AMB into ND decreases the ability of apoA-I to resist denaturation. Atomic force microscopy experiments showed that AMB induces compression of ND bilayer thickness while infrared spectroscopy analysis revealed that the presence of AMB does not induce extreme lipid disorder or alter the mean angle of the molecular axis along fatty acyl chains of ND phospholipids. Taken together the results are consistent with AMB-induced bilayer interdigitation, a phenomenon that likely contributes to AMB-dependent pore formation in susceptible membranes.",
keywords = "Amphotericin B, Atomic force microscopy, Infrared spectroscopy, Interdigitation, Membrane, Nanodisk",
author = "Nguyen, {Thanh Son} and Weers, {Paul M M} and Vincent Raussens and Zhen Wang and Gang Ren and Todd Sulchek and Hoeprich, {Paul D.} and Ryan, {Robert O.}",
year = "2008",
month = "1",
doi = "10.1016/j.bbamem.2007.10.005",
language = "English (US)",
volume = "1778",
pages = "303--312",
journal = "Biochimica et Biophysica Acta - Biomembranes",
issn = "0005-2736",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Amphotericin B induces interdigitation of apolipoprotein stabilized nanodisk bilayers

AU - Nguyen, Thanh Son

AU - Weers, Paul M M

AU - Raussens, Vincent

AU - Wang, Zhen

AU - Ren, Gang

AU - Sulchek, Todd

AU - Hoeprich, Paul D.

AU - Ryan, Robert O.

PY - 2008/1

Y1 - 2008/1

N2 - Amphotericin B nanodisks (AMB-ND) are ternary complexes of AMB, phospholipid and apolipoprotein organized as discrete nanometer scale disk-shaped bilayers. In gel filtration chromatography experiments, empty ND lacking AMB elute as a single population of particles with a molecular weight in the range of 200 kDa. AMB-ND formulated at a 4:1 phospholipid:AMB weight ratio separated into two peaks. One peak eluted at the position of control ND lacking AMB while the second peak, containing all of the AMB present in the original sample, eluted in the void volume. When ND prepared with increased AMB were subjected to gel filtration chromatography an increased proportion of phospholipid and apolipoprotein was recovered in the void volume with AMB. Native gradient gel electrophoresis corroborated the gel filtration chromatography data and electron microscopy studies revealed an AMB concentration-dependent heterogeneity in ND particle size. Stability studies revealed that introduction of AMB into ND decreases the ability of apoA-I to resist denaturation. Atomic force microscopy experiments showed that AMB induces compression of ND bilayer thickness while infrared spectroscopy analysis revealed that the presence of AMB does not induce extreme lipid disorder or alter the mean angle of the molecular axis along fatty acyl chains of ND phospholipids. Taken together the results are consistent with AMB-induced bilayer interdigitation, a phenomenon that likely contributes to AMB-dependent pore formation in susceptible membranes.

AB - Amphotericin B nanodisks (AMB-ND) are ternary complexes of AMB, phospholipid and apolipoprotein organized as discrete nanometer scale disk-shaped bilayers. In gel filtration chromatography experiments, empty ND lacking AMB elute as a single population of particles with a molecular weight in the range of 200 kDa. AMB-ND formulated at a 4:1 phospholipid:AMB weight ratio separated into two peaks. One peak eluted at the position of control ND lacking AMB while the second peak, containing all of the AMB present in the original sample, eluted in the void volume. When ND prepared with increased AMB were subjected to gel filtration chromatography an increased proportion of phospholipid and apolipoprotein was recovered in the void volume with AMB. Native gradient gel electrophoresis corroborated the gel filtration chromatography data and electron microscopy studies revealed an AMB concentration-dependent heterogeneity in ND particle size. Stability studies revealed that introduction of AMB into ND decreases the ability of apoA-I to resist denaturation. Atomic force microscopy experiments showed that AMB induces compression of ND bilayer thickness while infrared spectroscopy analysis revealed that the presence of AMB does not induce extreme lipid disorder or alter the mean angle of the molecular axis along fatty acyl chains of ND phospholipids. Taken together the results are consistent with AMB-induced bilayer interdigitation, a phenomenon that likely contributes to AMB-dependent pore formation in susceptible membranes.

KW - Amphotericin B

KW - Atomic force microscopy

KW - Infrared spectroscopy

KW - Interdigitation

KW - Membrane

KW - Nanodisk

UR - http://www.scopus.com/inward/record.url?scp=38149029146&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38149029146&partnerID=8YFLogxK

U2 - 10.1016/j.bbamem.2007.10.005

DO - 10.1016/j.bbamem.2007.10.005

M3 - Article

VL - 1778

SP - 303

EP - 312

JO - Biochimica et Biophysica Acta - Biomembranes

JF - Biochimica et Biophysica Acta - Biomembranes

SN - 0005-2736

IS - 1

ER -