Nanoaggregates of micropurified lipopolysaccharide identified using dynamic light scattering, zeta potential measurement, and TLR4 signaling activity

Anal Biochem. 2012 Nov 15;430(2):203-13. doi: 10.1016/j.ab.2012.08.027. Epub 2012 Sep 6.

Abstract

Nanoaggregates composed of selected glycoforms from Escherichia coli 055:B5 lipopolysaccharide (LPS) were prepared by combining sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, zinc-imidazole reverse staining, zinc chelation after cutting gel slices, elution with either 0.5% triethylamine (TEA) or 0.4% to 0.5% surfactant (SDS or deoxycholate [DOC]) from extrusion-generated gel microparticles, and centrifugal diafiltration after appropriate surfactant dilution. Dynamic light scattering allows detecting these aggregates, giving a size distribution from 10 to 100nm in diameter. The formation of the aggregates prepared with selected DOC-eluted LPS glycoforms was notably improved over those prepared with TEA-eluted glycoforms. As the O-side chain length increased in the composition of the former aggregates, there was a gradual decrease in the electrophoretic mobility (from -1.2 to 0.0110(-8)m(2)/Vs), giving a calculated zeta potential from -15 to 0.1mV at pH6.8. These aggregates were further characterized for their abilities to elicit agonistic effects on human Toll-like receptor 4, as shown by in vitro activation of nuclear factor kappa light chain enhancer of activated B cells (NF-κB) in engineered HEK293 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Deoxycholic Acid / chemistry
  • Electrophoresis, Polyacrylamide Gel
  • Escherichia coli / metabolism
  • Ethylamines / chemistry
  • HEK293 Cells
  • Humans
  • Light*
  • Lipopolysaccharides / analysis*
  • Nanostructures / chemistry*
  • Scattering, Radiation*
  • Signal Transduction
  • Sodium Dodecyl Sulfate / chemistry
  • Toll-Like Receptor 4 / agonists
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Ethylamines
  • Lipopolysaccharides
  • Toll-Like Receptor 4
  • Deoxycholic Acid
  • Sodium Dodecyl Sulfate
  • triethylamine