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

17 Scopus citations

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

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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., Hoeprich, P. D., & 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