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Poloxamer 407 and DMPC Form Large Lipid Nanodiscs: Structural Characterization Using Small-Angle X-ray Scattering.

Masakazu Fukuda1, Yuichi Takasaki2, Mizuho Ichihara1

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New lipid nanodiscs (LNDs) using poloxamer 407 and DMPC form larger discoidal structures. These nanodiscs offer potential for membrane protein research and temperature-responsive drug delivery systems.

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Area of Science:

  • Biophysics
  • Materials Science
  • Nanotechnology

Background:

  • Lipid nanodiscs (LNDs) are crucial for membrane protein studies and drug delivery.
  • Poloxamers offer tunable properties for nanostructure formation.

Purpose of the Study:

  • To structurally characterize LNDs formed by poloxamer 407 (PX407) and DMPC.
  • To evaluate PX407's efficacy in DMPC solubilization and nanodisc formation.
  • To explore the influence of salt concentration and polymer-to-lipid ratio on LND structure and stability.

Main Methods:

  • Small-angle X-ray scattering (SAXS) with core-shell bicelle-belt modeling.
  • Turbidity assessment.
  • Transmission electron microscopy (TEM).

Main Results:

  • PX407 demonstrated superior DMPC solubilization.
  • PX407-DMPC mixtures formed discoidal nanostructures with diameters of 17-30 nm.
  • Nanodisc dimensions and stability were tunable via salt concentration and polymer-to-lipid ratio.
  • Higher stability was achieved at a 2:1 PX407:DMPC mass ratio and ≥300 mM NaCl.
  • LNDs showed instability above DMPC's phase transition temperature (~24 °C).

Conclusions:

  • PX407-DMPC LNDs are larger than traditional styrene-maleic acid LNDs.
  • These LNDs possess tunable size and temperature-responsive characteristics.
  • Potential applications include membrane protein research needing large lipid platforms and temperature-sensitive delivery systems.